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    Kenneth L Rock MD

    TitleChair and Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentPathology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-2521
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

        Overview 
        Narrative

        Academic Background

        MD, 1978, University of Rochester

        Mechanisms to control display of foreign antigens to immune system

        Our laboratory investigates the mechanisms which control the display of foreign antigens to the immune system andDr. Kenneth Rock - Chair of the Pathology Department moregenerally the process of immune surveillance. In these processes the immune system uses MHC class I molecules to display on the cell surface oligopeptides derived from a cell's expressed genes. This allows cytotoxic T lymphocytes of the immune system to detect and eliminate cells expressing "foreign" sequences (e.g. from a viral infection or mutation). In many cases two distinct antigen presentation pathways are involved in the initial generation of the immune response and in the subsequent identification of the actual tumor or virally infected cell; these two pathways are termed cross presentation and direct presentation.

        To initiate responses, antigens must be displayed on class I molecules of professional antigen presenting cells (e.g. dendritic cells). If these cells are not themselves making the antigen, they acquire them from dying cells and present them on class I molecules, through a mechanism called “cross presentation”. In this process tissue antigens are internalized into phagosome of the antigen presenting cells and then can follow two distinct pathways for presentation. We are studying how the antigen presenting cells and their cross presentation pathways work and might be exploited for immunotherapy.

        Once cytotoxic T lymphocytes are stimulated they then seek out all cells that are synthesizing the "foreign antigen" and displaying its fragments on class I molecules. This display occurs through the “direct” or “classical” antigen presentation pathway. In this process, the majority of these MHC class I-presented peptides are generated by large proteolytic particles, proteasomes, which are present in the cytoplasm and nucleus of all Eukaryotic cells. These peptides must be of an exact size (8-10 residues) in order to bind to class I molecules. Where examined, the proteasome is responsible for making the proper C-terminal cleavage to produce antigenic peptides, however it often makes N-extended precursors. The precursor peptides can be trimmed to the mature epitope by aminopeptidases in the cytosol or endoplasmic reticulum or destroyed by other peptidases. After they are generated in the cytoplasm a fraction of the peptides are transported into the endoplasmic reticulum where ones of the correct size and sequence are bound by MHC class I molecules and transported to the cell surface for display. These processes determine whether antigens are recognized, the magnitude and specificity of the immune response and ultimately whether abnormal cells are eliminated. We are studying all of these processes in detail.

        A related area of investigation concerns how the immune surveillance process is regulated. In order for productive immune responses to be generated, it is necessary for antigen presenting cells to acquire not only antigen but also to mature to an immunostimulatory state. The latter occurs when the antigen presenting cell senses that an antigen is dangerous, e.g. associated with microbial components. In addition, danger signals can be generated by injured and dying cells. We have found that when cancerous or infected cells die they not only release antigens but also endogenous adjuvants that markedly stimulate the generation of T responses. These adjuvants are ordinarily sequestered in the cytosol and are released when the plasma membrane loses integrity. One of these endogenous adjuvants has been identified as uric acid and data suggests that the active form of this molecule is monosodium urate crystals (MSU). There are also other endogenous adjuvants. We are actively studying these molecules, how they function and their role in immune surveillance.



        Rotation Projects

        Potential Rotation Projects

        Rotations are available in Dr. Rock’s laboratory for graduate students in the GSBS program. The rotation projects will explore various aspects of how the immune system carries out surveillance to detect viral infections and cancers. Among the potential areas of research are: (1) The alarm signals that alert the immune system to potential danger; (2) The initial innate immune and inflammatory response to infection or other dangerous situations; (3) The biology of the sentinel cells (e.g. dendritic cells) that sense danger and report it the adaptive immune system; (4) The mechanisms by which sentinel cells (e.g. dendritic cells) acquire and display antigens to T cells; and, (5) The antigen presentation pathways by which virally infected or cancer cells display a sampling of their expressed gene products to the activated T cells. Specific rotation projects are chosen based on the student’s interests and state/availability of the various projects in the laboratory. The goals of rotations are for the student to gain knowledge in immunology, to learn how to approach experimental problems, to learn new techniques and methods, and to actually generate data that moves our knowledge forward. In addition, the rotation provides the student the opportunity to evaluate the laboratory as a possible place to conduct their thesis research in the future.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Rock for additional details.

        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Farfán-Arribas DJ, Stern LJ, Rock KL. Using intein catalysis to probe the origin of major histocompatibility complex class I-presented peptides. Proc Natl Acad Sci U S A. 2012 Oct 16; 109(42):16998-7003.
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        2. Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol. 2012 Sep 4; 9(1):13-23.
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        3. Kono H, Orlowski GM, Patel Z, Rock KL. The IL-1-Dependent Sterile Inflammatory Response Has a Substantial Caspase-1-Independent Component That Requires Cathepsin C. J Immunol. 2012 Oct 1; 189(7):3734-40.
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        4. Meriin AB, Mense M, Colbert JD, Liang F, Bihler H, Zaarur N, Rock KL, Sherman MY. A novel approach to recovery of function of mutant proteins by slowing down translation. J Biol Chem. 2012 Oct 5; 287(41):34264-72.
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        5. Janko M, Ontiveros F, Fitzgerald TJ, Deng A, Decicco M, Rock KL. IL-1 Generated Subsequent to Radiation-Induced Tissue Injury Contributes to the Pathogenesis of Radiodermatitis. Radiat Res. 2012 Sep; 178(3):166-72.
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        6. Rock K, McArdle O, Forde P, Dunne M, Fitzpatrick D, O'Neill B, Faul C. A clinical review of treatment outcomes in glioblastoma multiforme--the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival? Br J Radiol. 2012 Sep; 85(1017):e729-33.
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        7. Kincaid EZ, Che JW, York I, Escobar H, Reyes-Vargas E, Delgado JC, Welsh RM, Karow ML, Murphy AJ, Valenzuela DM, Yancopoulos GD, Rock KL. Mice completely lacking immunoproteasomes show major changes in antigen presentation. Nat Immunol. 2011; 13(2):129-35.
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        8. Jiang Z, Piao D, Bartels KE, Holyoak GR, Ritchey JW, Ownby CL, Rock K, Slobodov G. Transrectal ultrasound-integrated spectral optical tomography of hypoxic progression of a regressing tumor in a canine prostate. Technol Cancer Res Treat. 2011 Dec; 10(6):519-31.
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        9. Lu D, Yang X, Jiang NY, Woda BA, Liu Q, Dresser K, Mercurio AM, Rock KL, Jiang Z. IMP3, a New Biomarker to Predict Progression of Cervical Intraepithelial Neoplasia Into Invasive Cancer. Am J Surg Pathol. 2011 Nov; 35(11):1638-45.
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        10. Rock KL, Lai JJ, Kono H. Innate and adaptive immune responses to cell death. Immunol Rev. 2011 Sep; 243(1):191-205.
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        11. Hao S, Smith TW, Chu PG, Liu Q, Ok CY, Woda BA, Lu D, Lin P, Wang SA, Dresser K, Rock KL, Jiang Z. The Oncofetal Protein IMP3: A Novel Molecular Marker to Predict Aggressive Meningioma. Arch Pathol Lab Med. 2011 Aug; 135(8):1032-6.
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        12. Shi M, Fraire AE, Chu P, Cornejo K, Woda BA, Dresser K, Rock KL, Jiang Z. Oncofetal Protein IMP3, a New Diagnostic Biomarker to Distinguish Malignant Mesothelioma From Reactive Mesothelial Proliferation. Am J Surg Pathol. 2011 Jun; 35(6):878-82.
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        13. Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol. 2011 May; 18(5):604-13.
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        14. Menzies FM, Hourez R, Imarisio S, Raspe M, Sadiq O, Chandraratna D, O'Kane C, Rock KL, Reits E, Goldberg AL, Rubinsztein DC. Puromycin-sensitive aminopeptidase protects against aggregation-prone proteins via autophagy. Hum Mol Genet. 2010 Dec 1; 19(23):4573-86.
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        15. Georgiadou D, Hearn A, Evnouchidou I, Chroni A, Leondiadis L, York IA, Rock KL, Stratikos E. Placental leucine aminopeptidase efficiently generates mature antigenic peptides in vitro but in patterns distinct from endoplasmic reticulum aminopeptidase 1. J Immunol. 2010 Aug 1; 185(3):1584-92.
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        16. Kono H, Chen CJ, Ontiveros F, Rock KL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010 Jun 1; 120(6):1939-49.
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        17. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010 Apr 29; 464(7293):1357-61.
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        18. Hearn A, York IA, Bishop C, Rock KL. Characterizing the specificity and cooperation of aminopeptidases in the cytosol and endoplasmic reticulum during MHC class I antigen presentation. J Immunol. 2010 May 1; 184(9):4725-32.
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        19. Kono H, Karmarkar D, Iwakura Y, Rock KL. Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. J Immunol. 2010 Apr 15; 184(8):4470-8.
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        20. Rock KL, Latz E, Ontiveros F, Kono H. The sterile inflammatory response. Annu Rev Immunol. 2010 Mar; 28:321-42.
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        21. Rock KL, Farfán-Arribas DJ, Shen L. Proteases in MHC class I presentation and cross-presentation. J Immunol. 2010 Jan 1; 184(1):9-15.
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        22. Kawahara M, York IA, Hearn A, Farfan D, Rock KL. Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo. J Immunol. 2009 Nov 15; 183(10):6069-77.
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        23. Hearn A, York IA, Rock KL. The specificity of trimming of MHC class I-presented peptides in the endoplasmic reticulum. J Immunol. 2009 Nov 1; 183(9):5526-36.
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        24. Lu D, Vohra P, Chu PG, Woda B, Rock KL, Jiang Z. An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia. Am J Surg Pathol. 2009 Apr; 33(4):521-5.
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        25. Rock KL. Pathobiology of inflammation to cell death. Biol Blood Marrow Transplant. 2009 Jan; 15(1 Suppl):137-8.
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        26. Jiang Z, Chu PG, Woda BA, Liu Q, Balaji KC, Rock KL, Wu CL. Combination of quantitative IMP3 and tumor stage: a new system to predict metastasis for patients with localized renal cell carcinomas. Clin Cancer Res. 2008 Sep 1; 14(17):5579-84.
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        27. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008 Aug; 9(8):847-56.
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        28. Jiang Z, Lohse CM, Chu PG, Wu CL, Woda BA, Rock KL, Kwon ED. Oncofetal protein IMP3: a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas. Cancer. 2008 Jun 15; 112(12):2676-82.
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        29. Hernandez MG, Shen L, Rock KL. CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell help. J Immunol. 2008 Apr 1; 180(7):4382-90.
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        30. Sitnikova L, Mendese G, Liu Q, Woda BA, Lu D, Dresser K, Mohanty S, Rock KL, Jiang Z. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res. 2008 Mar 15; 14(6):1701-6.
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        31. Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008 Apr; 8(4):279-89.
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        32. Towne CF, York IA, Neijssen J, Karow ML, Murphy AJ, Valenzuela DM, Yancopoulos GD, Neefjes JJ, Rock KL. Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections. J Immunol. 2008 Feb 1; 180(3):1704-12.
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        33. Rock KL, Kono H. The inflammatory response to cell death. Annu Rev Pathol. 2008; 3:99-126.
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        34. Rock KL, Benacerraf B, Abbas AK. Pillars article: Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. 1984. J Immunol. 2007 Dec 1; 179(11):7194-205.
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        35. Li C, Zota V, Woda BA, Rock KL, Fraire AE, Jiang Z, Lu D, Xu B, Dresser K, Lutman CV, Fischer AH. Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations. Mod Pathol. 2007 Dec; 20(12):1263-8.
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        36. Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007 Jul; 13(7):851-6.
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        37. Towne CF, York IA, Watkin LB, Lazo JS, Rock KL. Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses. J Immunol. 2007 Jun 1; 178(11):6923-30.
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        38. Hernandez MG, Shen L, Rock KL. CD40-CD40 ligand interaction between dendritic cells and CD8+ T cells is needed to stimulate maximal T cell responses in the absence of CD4+ T cell help. J Immunol. 2007 Mar 1; 178(5):2844-52.
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        39. Li C, Rock KL, Woda BA, Jiang Z, Fraire AE, Dresser K. IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16(INK4a) expression. Mod Pathol. 2007 Feb; 20(2):242-7.
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        40. Rock KL. Exiting the outside world for cross-presentation. Immunity. 2006 Oct; 25(4):523-5.
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        41. Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock KL. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest. 2006 Aug; 116(8):2262-71.
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        42. York IA, Bhutani N, Zendzian S, Goldberg AL, Rock KL. Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentation. J Immunol. 2006 Aug 1; 177(3):1434-43.
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        43. Jiang Z, Chu PG, Woda BA, Rock KL, Liu Q, Hsieh CC, Li C, Chen W, Duan HO, McDougal S, Wu CL. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol. 2006 Jul; 7(7):556-64.
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        44. York IA, Brehm MA, Zendzian S, Towne CF, Rock KL. Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance. Proc Natl Acad Sci U S A. 2006 Jun 13; 103(24):9202-7.
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        45. Shi Y, Galusha SA, Rock KL. Cutting edge: elimination of an endogenous adjuvant reduces the activation of CD8 T lymphocytes to transplanted cells and in an autoimmune diabetes model. J Immunol. 2006 Apr 1; 176(7):3905-8.
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        46. Shen L, Rock KL. Priming of T cells by exogenous antigen cross-presented on MHC class I molecules. Curr Opin Immunol. 2006 Feb; 18(1):85-91.
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        47. Towne CF, York IA, Neijssen J, Karow ML, Murphy AJ, Valenzuela DM, Yancopoulos GD, Neefjes JJ, Rock KL. Leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for MHC class I antigen presentation. J Immunol. 2005 Nov 15; 175(10):6605-14.
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        48. Rock KL, Shen L. Cross-presentation: underlying mechanisms and role in immune surveillance. Immunol Rev. 2005 Oct; 207:166-83.
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        49. Pozzi LA, Maciaszek JW, Rock KL. Both dendritic cells and macrophages can stimulate naive CD8 T cells in vivo to proliferate, develop effector function, and differentiate into memory cells. J Immunol. 2005 Aug 15; 175(4):2071-81.
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        50. Retter MW, Johnson JC, Peckham DW, Bannink JE, Bangur CS, Dresser K, Cai F, Foy TM, Fanger NA, Fanger GR, Woda B, Rock KL. Characterization of a proapoptotic antiganglioside GM2 monoclonal antibody and evaluation of its therapeutic effect on melanoma and small cell lung carcinoma xenografts. Cancer Res. 2005 Jul 15; 65(14):6425-34.
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        51. York IA, Grant EP, Dahl AM, Rock KL. A mutant cell with a novel defect in MHC class I quality control. J Immunol. 2005 Jun 1; 174(11):6839-46.
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        52. Yantiss RK, Woda BA, Fanger GR, Kalos M, Whalen GF, Tada H, Andersen DK, Rock KL, Dresser K. KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. Am J Surg Pathol. 2005 Feb; 29(2):188-95.
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        53. Ciampa A, Fanger G, Khan A, Rock KL, Xu B. Mammaglobin and CRxA-01 in pleural effusion cytology: potential utility of distinguishing metastatic breast carcinomas from other cytokeratin 7-positive/cytokeratin 20-negative carcinomas. Cancer. 2004 Dec 25; 102(6):368-72.
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        54. Rock KL, Hearn A, Chen CJ, Shi Y. Natural endogenous adjuvants. Springer Semin Immunopathol. 2005 Jan; 26(3):231-46.
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        55. Jiang Z, Wu CL, Woda BA, Iczkowski KA, Chu PG, Tretiakova MS, Young RH, Weiss LM, Blute RD, Brendler CB, Krausz T, Xu JC, Rock KL, Amin MB, Yang XJ. Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker. Histopathology. 2004 Sep; 45(3):218-25.
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        56. Shen L, Sigal LJ, Boes M, Rock KL. Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Immunity. 2004 Aug; 21(2):155-65.
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        57. Rock KL, York IA, Goldberg AL. Post-proteasomal antigen processing for major histocompatibility complex class I presentation. Nat Immunol. 2004 Jul; 5(7):670-7.
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        58. Shen L, Rock KL. Cellular protein is the source of cross-priming antigen in vivo. Proc Natl Acad Sci U S A. 2004 Mar 2; 101(9):3035-40.
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        59. Rock KL. The ins and outs of cross-presentation. Nat Immunol. 2003 Oct; 4(10):941-3.
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        60. Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003 Oct 2; 425(6957):516-21.
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        61. York IA, Mo AX, Lemerise K, Zeng W, Shen Y, Abraham CR, Saric T, Goldberg AL, Rock KL. The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentation. Immunity. 2003 Mar; 18(3):429-40.
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        62. Jiang Z, Fanger GR, Banner BF, Woda BA, Algate P, Dresser K, Xu J, Reed SG, Rock KL, Chu PG. A dietary enzyme: alpha-methylacyl-CoA racemase/P504S is overexpressed in colon carcinoma. Cancer Detect Prev. 2003; 27(6):422-6.
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        63. Saric T, Chang SC, Hattori A, York IA, Markant S, Rock KL, Tsujimoto M, Goldberg AL. An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Nat Immunol. 2002 Dec; 3(12):1169-76.
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        64. York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, Rock KL. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol. 2002 Dec; 3(12):1177-84.
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        65. Goldberg AL, Cascio P, Saric T, Rock KL. The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol Immunol. 2002 Oct; 39(3-4):147-64.
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        66. Goldberg AL, Rock K. Not just research tools--proteasome inhibitors offer therapeutic promise. Nat Med. 2002 Apr; 8(4):338-40.
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        67. Rock KL, York IA, Saric T, Goldberg AL. Protein degradation and the generation of MHC class I-presented peptides. Adv Immunol. 2002; 80:1-70.
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        68. Shi Y, Rock KL. Cell death releases endogenous adjuvants that selectively enhance immune surveillance of particulate antigens. Eur J Immunol. 2002 Jan; 32(1):155-62.
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        69. Jiang Z, Woda BA, Rock KL, Xu Y, Savas L, Khan A, Pihan G, Cai F, Babcook JS, Rathanaswami P, Reed SG, Xu J, Fanger GR. P504S: a new molecular marker for the detection of prostate carcinoma. Am J Surg Pathol. 2001 Nov; 25(11):1397-404.
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        70. Saric T, Beninga J, Graef CI, Akopian TN, Rock KL, Goldberg AL. Major histocompatibility complex class I-presented antigenic peptides are degraded in cytosolic extracts primarily by thimet oligopeptidase. J Biol Chem. 2001 Sep 28; 276(39):36474-81.
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        71. Cascio P, Hilton C, Kisselev AF, Rock KL, Goldberg AL. 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide. EMBO J. 2001 May 15; 20(10):2357-66.
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        72. Hilton CJ, Dahl AM, Rock KL. Anti-peptide antibody blocks peptide binding to MHC class I molecules in the endoplasmic reticulum. J Immunol. 2001 Mar 15; 166(6):3952-6.
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        73. Shi Y, Zheng W, Rock KL. Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses. Proc Natl Acad Sci U S A. 2000 Dec 19; 97(26):14590-5.
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        74. Sigal LJ, Rock KL. Bone marrow-derived antigen-presenting cells are required for the generation of cytotoxic T lymphocyte responses to viruses and use transporter associated with antigen presentation (TAP)-dependent and -independent pathways of antigen presentation. J Exp Med. 2000 Oct 16; 192(8):1143-50.
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        75. Fernandes DM, Vidard L, Rock KL. Characterization of MHC class II-presented peptides generated from an antigen targeted to different endocytic compartments. Eur J Immunol. 2000 Aug; 30(8):2333-43.
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        76. Mo AX, van Lelyveld SF, Craiu A, Rock KL. Sequences that flank subdominant and cryptic epitopes influence the proteolytic generation of MHC class I-presented peptides. J Immunol. 2000 Apr 15; 164(8):4003-10.
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        77. Mo XY, Cascio P, Lemerise K, Goldberg AL, Rock K. Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides. J Immunol. 1999 Dec 1; 163(11):5851-9.
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        78. York IA, Goldberg AL, Mo XY, Rock KL. Proteolysis and class I major histocompatibility complex antigen presentation. Immunol Rev. 1999 Dec; 172:49-66.
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        79. Fernandes DM, Baird AM, Berg LJ, Rock KL. A monoclonal antibody reactive with a 40-kDa molecule on fetal thymocytes and tumor cells blocks proliferation and stimulates aggregation and apoptosis. J Immunol. 1999 Aug 1; 163(3):1306-14.
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        80. Sigal LJ, Crotty S, Andino R, Rock KL. Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature. 1999 Mar 4; 398(6722):77-80.
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        81. Russell HI, York IA, Rock KL, Monaco JJ. Class II antigen processing defects in two H2d mouse cell lines are caused by point mutations in the H2-DMa gene. Eur J Immunol. 1999 Mar; 29(3):905-11.
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        82. Rock KL, Goldberg AL. Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol. 1999; 17:739-79.
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        83. Raychaudhuri S, Rock KL. Fully mobilizing host defense: building better vaccines. Nat Biotechnol. 1998 Nov; 16(11):1025-31.
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        84. Sigal LJ, Reiser H, Rock KL. The role of B7-1 and B7-2 costimulation for the generation of CTL responses in vivo. J Immunol. 1998 Sep 15; 161(6):2740-5.
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        85. Beninga J, Rock KL, Goldberg AL. Interferon-gamma can stimulate post-proteasomal trimming of the N terminus of an antigenic peptide by inducing leucine aminopeptidase. J Biol Chem. 1998 Jul 24; 273(30):18734-42.
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        86. Mandl S, Sigal LJ, Rock KL, Andino R. Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect mice against lethal challenge with malignant melanoma cells expressing a model antigen. Proc Natl Acad Sci U S A. 1998 Jul 7; 95(14):8216-21.
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        87. Henderson SC, Berezovskaya A, English A, Palliser D, Rock KL, Bamezai A. CD4+ T cells mature in the absence of MHC class I and class II expression in Ly-6A.2 transgenic mice. J Immunol. 1998 Jul 1; 161(1):175-82.
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        88. Mazzaccaro RJ, Stenger S, Rock KL, Porcelli SA, Brenner MB, Modlin RL, Bloom BR. Cytotoxic T lymphocytes in resistance to tuberculosis. Adv Exp Med Biol. 1998; 452:85-101.
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        89. Craiu A, Akopian T, Goldberg A, Rock KL. Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide. Proc Natl Acad Sci U S A. 1997 Sep 30; 94(20):10850-5.
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        90. Craiu A, Gaczynska M, Akopian T, Gramm CF, Fenteany G, Goldberg AL, Rock KL. Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation. J Biol Chem. 1997 May 16; 272(20):13437-45.
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        91. Shen Z, Reznikoff G, Dranoff G, Rock KL. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J Immunol. 1997 Mar 15; 158(6):2723-30.
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        92. Mazzaccaro RJ, Gedde M, Jensen ER, van Santen HM, Ploegh HL, Rock KL, Bloom BR. Major histocompatibility class I presentation of soluble antigen facilitated by Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 1996 Oct 15; 93(21):11786-91.
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        93. Gaczynska M, Goldberg AL, Tanaka K, Hendil KB, Rock KL. Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-gamma-induced subunits LMP2 and LMP7. J Biol Chem. 1996 Jul 19; 271(29):17275-80.
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        94. Michalek MT, Grant EP, Rock KL. Chemical denaturation and modification of ovalbumin alters its dependence on ubiquitin conjugation for class I antigen presentation. J Immunol. 1996 Jul 15; 157(2):617-24.
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        95. Rock KL, Clark K. Analysis of the role of MHC class II presentation in the stimulation of cytotoxic T lymphocytes by antigens targeted into the exogenous antigen-MHC class I presentation pathway. J Immunol. 1996 May 15; 156(10):3721-6.
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        96. Vidard L, Kovacsovics-Bankowski M, Kraeft SK, Chen LB, Benacerraf B, Rock KL. Analysis of MHC class II presentation of particulate antigens of B lymphocytes. J Immunol. 1996 Apr 15; 156(8):2809-18.
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        97. Rock KL. A new foreign policy: MHC class I molecules monitor the outside world. Immunol Today. 1996 Mar; 17(3):131-7.
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        98. York IA, Rock KL. Antigen processing and presentation by the class I major histocompatibility complex. Annu Rev Immunol. 1996; 14:369-96.
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        99. Grant EP, Michalek MT, Goldberg AL, Rock KL. Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC class I presentation. J Immunol. 1995 Oct 15; 155(8):3750-8.
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        100. Falo LD, Kovacsovics-Bankowski M, Thompson K, Rock KL. Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity. Nat Med. 1995 Jul; 1(7):649-53.
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        101. Bamezai A, Rock KL. Overexpressed Ly-6A.2 mediates cell-cell adhesion by binding a ligand expressed on lymphoid cells. Proc Natl Acad Sci U S A. 1995 May 9; 92(10):4294-8.
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        102. Bamezai A, Palliser D, Berezovskaya A, McGrew J, Higgins K, Lacy E, Rock KL. Regulated expression of Ly-6A.2 is important for T cell development. J Immunol. 1995 May 1; 154(9):4233-9.
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        103. Lah TT, Hawley M, Rock KL, Goldberg AL. Gamma-interferon causes a selective induction of the lysosomal proteases, cathepsins B and L, in macrophages. FEBS Lett. 1995 Apr 17; 363(1-2):85-9.
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        104. Kovacsovics-Bankowski M, Rock KL. A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science. 1995 Jan 13; 267(5195):243-6.
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        105. Goldberg AL, Gaczynska M, Grant E, Michalek M, Rock KL. Functions of the proteasome in antigen presentation. Cold Spring Harb Symp Quant Biol. 1995; 60:479-90.
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        106. Van Kaer L, Ashton-Rickardt PG, Eichelberger M, Gaczynska M, Nagashima K, Rock KL, Goldberg AL, Doherty PC, Tonegawa S. Altered peptidase and viral-specific T cell response in LMP2 mutant mice. Immunity. 1994 Oct; 1(7):533-41.
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        107. Kovacsovics-Bankowski M, Rock KL. Presentation of exogenous antigens by macrophages: analysis of major histocompatibility complex class I and II presentation and regulation by cytokines. Eur J Immunol. 1994 Oct; 24(10):2421-8.
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        108. Gaczynska M, Rock KL, Spies T, Goldberg AL. Peptidase activities of proteasomes are differentially regulated by the major histocompatibility complex-encoded genes for LMP2 and LMP7. Proc Natl Acad Sci U S A. 1994 Sep 27; 91(20):9213-7.
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        109. Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9; 78(5):761-71.
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        110. Bamezai A, Rock KL. A role of Ly-6A.2 in T lymphocyte activation and development. Braz J Med Biol Res. 1994 Feb; 27(2):283-8.
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        111. Gaczynska M, Rock KL, Goldberg AL. Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature. 1993 Sep 16; 365(6443):264-7.
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        112. Michalek MT, Grant EP, Gramm C, Goldberg AL, Rock KL. A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation. Nature. 1993 Jun 10; 363(6429):552-4.
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        113. Kovacsovics-Bankowski M, Clark K, Benacerraf B, Rock KL. Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc Natl Acad Sci U S A. 1993 Jun 1; 90(11):4942-6.
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        114. Dang LH, Lien LL, Benacerraf B, Rock KL. A mutant antigen-presenting cell defective in antigen presentation expresses class II MHC molecules with an altered conformation. J Immunol. 1993 May 15; 150(10):4206-17.
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        115. Rock KL, Fleischacker C, Gamble S. Peptide-priming of cytolytic T cell immunity in vivo using beta 2-microglobulin as an adjuvant. J Immunol. 1993 Feb 15; 150(4):1244-52.
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        116. Rock KL, Rothstein L, Gamble S, Fleischacker C. Characterization of antigen-presenting cells that present exogenous antigens in association with class I MHC molecules. J Immunol. 1993 Jan 15; 150(2):438-46.
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        117. Gaczynska M, Rock KL, Goldberg AL. Role of proteasomes in antigen presentation. Enzyme Protein. 1993; 47(4-6):354-69.
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        118. Rock KL, Rothstein L, Benacerraf B. Analysis of the association of peptides of optimal length to class I molecules on the surface of cells. Proc Natl Acad Sci U S A. 1992 Oct 1; 89(19):8918-22.
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        119. Vidard L, Rock KL, Benacerraf B. Heterogeneity in antigen processing by different types of antigen-presenting cells. Effect of cell culture on antigen processing ability. J Immunol. 1992 Sep 15; 149(6):1905-11.
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        120. Falo LD, Colarusso LJ, Benacerraf B, Rock KL. Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1992 Sep 1; 89(17):8347-50.
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        121. Vidard L, Rock KL, Couderc J, Mouton D, Benacerral B. Processing and presentation of ovalbumin in mice genetically selected for antibody response. Eur J Immunol. 1992 Aug; 22(8):2165-8.
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        122. Vidard L, Rock KL, Benacerraf B. Diversity in MHC class II ovalbumin T cell epitopes generated by distinct proteases. J Immunol. 1992 Jul 15; 149(2):498-504.
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        123. Goldberg AL, Rock KL. Proteolysis, proteasomes and antigen presentation. Nature. 1992 Jun 4; 357(6377):375-9.
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        124. Rock KL, Rothstein L, Fleischacker C, Gamble S. Inhibition of class I and class II MHC-restricted antigen presentation by cytotoxic T lymphocytes specific for an exogenous antigen. J Immunol. 1992 May 15; 148(10):3028-33.
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        125. Rock KL, Rothstein L, Gamble S, Gramm C, Benacerraf B. Chemical cross-linking of class I molecules on cells creates receptive peptide binding sites. J Immunol. 1992 Mar 1; 148(5):1451-7.
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        126. Michalek MT, Benacerraf B, Rock KL. The class II MHC-restricted presentation of endogenously synthesized ovalbumin displays clonal variation, requires endosomal/lysosomal processing, and is up-regulated by heat shock. J Immunol. 1992 Feb 15; 148(4):1016-24.
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        127. Bamezai A, Goldmacher VS, Rock KL. Internalization of glycosyl-phosphatidylinositol (GPI)-anchored lymphocyte proteins. II. GPI-anchored and transmembrane molecules internalize through distinct pathways. Eur J Immunol. 1992 Jan; 22(1):15-21.
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        128. Grant EP, Rock KL. MHC class I-restricted presentation of exogenous antigen by thymic antigen-presenting cells in vitro and in vivo. J Immunol. 1992 Jan 1; 148(1):13-8.
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        129. McGrew JT, Rock KL. Stimulation of human Jurkat cells by monoclonal antibody crosslinking of transfected-Ly-6A.2 (TAP) molecules. Cell Immunol. 1991 Oct 1; 137(1):118-26.
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        130. Vidard L, Rock KL, Benacerraf B. The generation of immunogenic peptides can be selectively increased or decreased by proteolytic enzyme inhibitors. J Immunol. 1991 Sep 15; 147(6):1786-91.
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        131. Bamezai A, Rock KL. Effect of ras-activation on the expression of glycosyl-phosphatidylinositol-anchored proteins on the plasma membrane. Oncogene. 1991 Aug; 6(8):1445-51.
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        132. Pinto VB, Rock KL. Characterization of the proliferative response of a CD4-8- thymic T lymphoma cell line to stimulation by thymic cellular elements. J Immunol. 1991 Jul 1; 147(1):42-9.
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        133. Rock KL, Gamble S, Rothstein L, Gramm C, Benacerraf B. Dissociation of beta 2-microglobulin leads to the accumulation of a substantial pool of inactive class I MHC heavy chains on the cell surface. Cell. 1991 May 17; 65(4):611-20.
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        134. Dang LH, Rock KL. Stimulation of B lymphocytes through surface Ig receptors induces LFA-1 and ICAM-1-dependent adhesion. J Immunol. 1991 May 15; 146(10):3273-9.
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        135. Rock KL, Gramm C, Benacerraf B. Low temperature and peptides favor the formation of class I heterodimers on RMA-S cells at the cell surface. Proc Natl Acad Sci U S A. 1991 May 15; 88(10):4200-4.
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        136. McGrew JT, Rock KL. Isolation, expression, and sequence of the TAP/Ly-6A.2 chromosomal gene. J Immunol. 1991 May 15; 146(10):3633-8.
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        137. Michalek MT, Benacerraf B, Rock KL. Weak base amines can inhibit class I MHC-restricted antigen presentation. J Immunol. 1991 Jan 15; 146(2):449-56.
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        138. Rock KL, Gamble S, Rothstein L, Benacerraf B. Reassociation with beta 2-microglobulin is necessary for Db class I major histocompatibility complex binding of an exogenous influenza peptide. Proc Natl Acad Sci U S A. 1991 Jan 1; 88(1):301-4.
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        139. Rock KL, Rothstein LE, Gamble SR, Benacerraf B. Reassociation with beta 2-microglobulin is necessary for Kb class I major histocompatibility complex binding of exogenous peptides. Proc Natl Acad Sci U S A. 1990 Oct; 87(19):7517-21.
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        140. Rock KL, Gamble S, Rothstein L. Presentation of exogenous antigen with class I major histocompatibility complex molecules. Science. 1990 Aug 24; 249(4971):918-21.
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        141. Rock KL, Rothstein L, Gamble S. Generation of class I MHC-restricted T-T hybridomas. J Immunol. 1990 Aug 1; 145(3):804-11.
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        142. Dang LH, Michalek MT, Takei F, Benaceraff B, Rock KL. Role of ICAM-1 in antigen presentation demonstrated by ICAM-1 defective mutants. J Immunol. 1990 Jun 1; 144(11):4082-91.
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        143. Bamezai A, Goldmacher V, Reiser H, Rock KL. Internalization of phosphatidylinositol-anchored lymphocyte proteins. I. Documentation and potential significance for T cell stimulation. J Immunol. 1989 Nov 15; 143(10):3107-16.
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        144. Rock KL, Reiser H, Bamezai A, McGrew J, Benacerraf B. The LY-6 locus: a multigene family encoding phosphatidylinositol-anchored membrane proteins concerned with T-cell activation. Immunol Rev. 1989 Oct; 111:195-224.
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        145. Michalek MT, Benacerraf B, Rock KL. Two genetically identical antigen-presenting cell clones display heterogeneity in antigen processing. Proc Natl Acad Sci U S A. 1989 May; 86(9):3316-20.
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        146. Benacerraf B, Michalek MT, Dang LH, Rock KL. The importance of antigen processing in determinant selection and of the cell membrane as a reservoir of processed antigen. Cold Spring Harb Symp Quant Biol. 1989; 54 Pt 1:293-8.
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        147. Bamezai A, Reiser H, Rock KL. T cell receptor/CD3 negative variants are unresponsive to stimulation through the Ly-6 encoded molecule, TAP. J Immunol. 1988 Sep 1; 141(5):1423-8.
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        148. Reiser H, Coligan J, Palmer E, Benacerraf B, Rock KL. Cloning and expression of a cDNA for the T-cell-activating protein TAP. Proc Natl Acad Sci U S A. 1988 Apr; 85(7):2255-9.
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        149. Yeh ET, Reiser H, Bamezai A, Rock KL. TAP transcription and phosphatidylinositol linkage mutants are defective in activation through the T cell receptor. Cell. 1988 Mar 11; 52(5):665-74.
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        150. Reiser H, Yeh ET, Coligan J, Benacerraf B, Rock KL. Structure and function of the TAP protein and related Ly-6-linked molecules. Year Immunol. 1988; 3:80-8.
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        151. Falo LD, Benacerraf B, Rothstein L, Rock KL. Cerulenin is a potent inhibitor of antigen processing by antigen-presenting cells. J Immunol. 1987 Dec 15; 139(12):3918-23.
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        152. Reiser H, Coligan J, Benacerraf B, Rock KL. Biosynthesis, glycosylation, and partial N-terminal amino acid sequence of the T-cell-activating protein TAP. Proc Natl Acad Sci U S A. 1987 May; 84(10):3370-4.
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        153. Yeh ET, Reiser H, Daley J, Rock KL. Stimulation of T cells via the TAP molecule, a member in a family of activating proteins encoded in the Ly-6 locus. J Immunol. 1987 Jan 1; 138(1):91-7.
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        154. Falo LD, Haber SI, Herrmann S, Benacerraf B, Rock KL. Characterization of antigen association with accessory cells: specific removal of processed antigens from the cell surface by phospholipases. Proc Natl Acad Sci U S A. 1987 Jan; 84(2):522-6.
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        155. Yeh ET, Reiser H, Benacerraf B, Rock KL. T cell-activating protein on murine lymphocytes. Fed Proc. 1986 Dec; 45(13):2991-4.
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        156. Reiser H, Oettgen H, Yeh ET, Terhorst C, Low MG, Benacerraf B, Rock KL. Structural characterization of the TAP molecule: a phosphatidylinositol-linked glycoprotein distinct from the T cell receptor/T3 complex and Thy-1. Cell. 1986 Nov 7; 47(3):365-70.
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        157. Rock KL, Haber SI, Liano D, Benacerraf B, Abbas AK. Antigen presentation by hapten-specific B lymphocytes. III. Analysis of the immunoglobulin-dependent pathway of antigen presentation to interleukin 1-dependent T lymphocytes. Eur J Immunol. 1986 Nov; 16(11):1407-12.
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        158. Yeh ET, Reiser H, Benacerraf B, Rock KL. Expression of T-cell-activating protein in peripheral lymphocyte subsets. Proc Natl Acad Sci U S A. 1986 Oct; 83(19):7424-8.
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        159. Falo LD, Benacerraf B, Rock KL. Phospholipase treatment of accessory cells that have been exposed to antigen selectively inhibits antigen-specific Ia-restricted, but not allospecific, stimulation of T lymphocytes. Proc Natl Acad Sci U S A. 1986 Sep; 83(18):6994-7.
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        160. Yeh ET, Reiser H, Benacerraf B, Rock KL. The expression, function, and ontogeny of a novel T cell-activating protein, TAP, in the thymus. J Immunol. 1986 Aug 15; 137(4):1232-8.
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        161. Reiser H, Yeh ET, Gramm CF, Benacerraf B, Rock KL. Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus. Proc Natl Acad Sci U S A. 1986 May; 83(9):2954-8.
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        162. Rock KL, Yeh ET, Gramm CF, Haber SI, Reiser H, Benacerraf B. TAP, a novel T cell-activating protein involved in the stimulation of MHC-restricted T lymphocytes. J Exp Med. 1986 Feb 1; 163(2):315-33.
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        163. Falo LD, Sullivan K, Benacerraf B, Mescher MF, Rock KL. Analysis of antigen presentation by metabolically inactive accessory cells and their isolated membranes. Proc Natl Acad Sci U S A. 1985 Oct; 82(19):6647-51.
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        164. Abbas AK, Haber S, Rock KL. Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors. J Immunol. 1985 Sep; 135(3):1661-7.
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        165. Rock KL. Self antigenic mimicry and Ir gene control of T cell responsiveness--a commentary. J Mol Cell Immunol. 1985; 2(2):80-1.
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        166. Rock KL, Benacerraf B. Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. II. Competitive inhibition of I-E-restricted, antigen-specific T cell responses. J Exp Med. 1984 Dec 1; 160(6):1864-79.
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        167. Rock KL, Benacerraf B, Abbas AK. Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J Exp Med. 1984 Oct 1; 160(4):1102-13.
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        168. Yeh ET, Benacerraf B, Rock KL. Analysis of thymocyte MHC specificity with thymocyte hybridomas. J Exp Med. 1984 Sep 1; 160(3):799-813.
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        169. Benacerraf B, Rock KL. The interaction between class II MHC molecules and antigens as a basis for Ir gene specificity. Ann Immunol (Paris). 1984 May-Jun; 135C(3):386-9.
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        170. Rock KL, Benacerraf B. The role of Ia molecules in the activation of T lymphocytes. IV. The basis of the thymocyte IL 1 response and its possible role in the generation of the T cell repertoire. J Immunol. 1984 Apr; 132(4):1654-62.
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        171. Rock KL, Benacerraf B. Selective modification of a private I-A allo-stimulating determinant(s) upon association of antigen with an antigen-presenting cell. J Exp Med. 1984 Apr 1; 159(4):1238-52.
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        172. Rock KL, Benacerraf B. Thymic T cells are driven to expand upon interaction with self-class II major histocompatibility complex gene products on accessory cells. Proc Natl Acad Sci U S A. 1984 Feb; 81(4):1221-4.
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        173. Rock KL, Yeh ET, Benacerraf B. Selection of thymocyte MHC restriction specificity in vitro. J Mol Cell Immunol. 1984; 1(5):311-20.
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        174. Rock KL, Benacerraf B. Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation. J Exp Med. 1983 May 1; 157(5):1618-34.
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        175. Rock KL, Benacerraf B. MHC-restricted T cell activation: analysis with T cell hybridomas. Immunol Rev. 1983; 76:29-57.
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        176. Rock KL, Benacerraf B. The role of Ia molecules in the activation of T lymphocytes. III. Antigen-specific, Ia-restricted, interleukin 2-producing T cell hybridomas with detectable affinity for the restricting I-A molecule. J Exp Med. 1983 Jan 1; 157(1):359-64.
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        177. Rock KL, Barnes MC, Germain RN, Benacerraf B. The role of Ia molecules in the activation of T lymphocytes. II. Ia-restricted recognition of allo K/D antigens is required for class I MHC-stimulated mixed lymphocyte responses. J Immunol. 1983 Jan; 130(1):457-62.
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        178. Rock KL. The role of Ia molecules in the activation of T lymphocytes. I. The activation of an IL 1-dependent IL 2-producing T cell hybridoma by Con A requires an interaction, which is not H-2-restricted, with an Ia-bearing accessory cell. J Immunol. 1982 Oct; 129(4):1360-6.
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        179. Sy MS, Lee SH, Tsurufuji M, Rock KL, Benacerraf B, Finberg R. Two distinct mechanisms regulate the in vivo generation of cytotoxic T cells. J Exp Med. 1982 Sep 1; 156(3):918-23.
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        180. Letvin NL, Rock KL, Nepom JT, Gramm CF, Benacerraf B. Antibody responses to trinitrophenyl (TNP)-L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in microcultures: anti-hapten and anti-carrier responses appear to be under separable control. Cell Immunol. 1982 Jul 15; 71(1):89-98.
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        181. Swierkosz JE, Rock K, Marrack P, Kappler JW. The role of H-2 linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper T cells each specific for antigen and one set of parental H-2 products. J Exp Med. 1978 Feb 1; 147(2):554-70.
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