Header Logo

Search Result Details

This page shows the details of why an item matched the keywords from your search.
One or more keywords matched the following properties of Rock, Kenneth

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.

One or more keywords matched the following items that are connected to Rock, Kenneth
Item TypeName
Academic Article Analysis of MHC class II presentation of particulate antigens of B lymphocytes.
Academic Article 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.
Academic Article A new foreign policy: MHC class I molecules monitor the outside world.
Academic Article Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect mice against lethal challenge with malignant melanoma cells expressing a model antigen.
Academic Article Antigen processing and presentation by the class I major histocompatibility complex.
Academic Article Chemical denaturation and modification of ovalbumin alters its dependence on ubiquitin conjugation for class I antigen presentation.
Academic Article Heterogeneity in antigen processing by different types of antigen-presenting cells. Effect of cell culture on antigen processing ability.
Academic Article Sequences that flank subdominant and cryptic epitopes influence the proteolytic generation of MHC class I-presented peptides.
Academic Article Functions of the proteasome in antigen presentation.
Academic Article Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules.
Academic Article Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation.
Academic Article Fully mobilizing host defense: building better vaccines.
Academic Article The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentation.
Academic Article Cytotoxic T lymphocytes in resistance to tuberculosis.
Academic Article Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen.
Academic Article Class II antigen processing defects in two H2d mouse cell lines are caused by point mutations in the H2-DMa gene.
Academic Article Cellular protein is the source of cross-priming antigen in vivo.
Academic Article Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo.
Academic Article Degradation of cell proteins and the generation of MHC class I-presented peptides.
Academic Article Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides.
Academic Article Proteolysis and class I major histocompatibility complex antigen presentation.
Academic Article Both dendritic cells and macrophages can stimulate naive CD8 T cells in vivo to proliferate, develop effector function, and differentiate into memory cells.
Academic Article Cross-presentation: underlying mechanisms and role in immune surveillance.
Academic Article Leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for MHC class I antigen presentation.
Academic Article Priming of T cells by exogenous antigen cross-presented on MHC class I molecules.
Academic Article Characterization of MHC class II-presented peptides generated from an antigen targeted to different endocytic compartments.
Academic Article Inhibition of class I and class II MHC-restricted antigen presentation by cytotoxic T lymphocytes specific for an exogenous antigen.
Academic Article 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.
Academic Article Anti-peptide antibody blocks peptide binding to MHC class I molecules in the endoplasmic reticulum.
Academic Article Exiting the outside world for cross-presentation.
Academic Article Pillars article: antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. 1984.
Academic Article Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections.
Academic Article Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors.
Academic Article Analysis of antigen presentation by metabolically inactive accessory cells and their isolated membranes.
Academic Article The specificity of trimming of MHC class I-presented peptides in the endoplasmic reticulum.
Academic Article Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo.
Academic Article Characterizing the specificity and cooperation of aminopeptidases in the cytosol and endoplasmic reticulum during MHC class I antigen presentation.
Academic Article Placental leucine aminopeptidase efficiently generates mature antigenic peptides in vitro but in patterns distinct from endoplasmic reticulum aminopeptidase 1.
Academic Article Protein degradation and the generation of MHC class I-presented peptides.
Academic Article Using intein catalysis to probe the origin of major histocompatibility complex class I-presented peptides.
Academic Article The ins and outs of cross-presentation.
Academic Article Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation.
Academic Article Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors.
Academic Article Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC class I presentation.
Academic Article Proteolysis, proteasomes and antigen presentation.
Academic Article Post-proteasomal antigen processing for major histocompatibility complex class I presentation.
Academic Article Role of ICAM-1 in antigen presentation demonstrated by ICAM-1 defective mutants.
Academic Article Weak base amines can inhibit class I MHC-restricted antigen presentation.
Academic Article Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentation.
Academic Article Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses.
Academic Article Two genetically identical antigen-presenting cell clones display heterogeneity in antigen processing.
Academic Article Proteases in MHC class I presentation and cross-presentation.
Academic Article Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1.
Academic Article The importance of antigen processing in determinant selection and of the cell membrane as a reservoir of processed antigen.
Academic Article Mice completely lacking immunoproteasomes show major changes in antigen presentation.
Academic Article Antigen presentation by hapten-specific B lymphocytes. III. Analysis of the immunoglobulin-dependent pathway of antigen presentation to interleukin 1-dependent T lymphocytes.
Academic Article Cerulenin is a potent inhibitor of antigen processing by antigen-presenting cells.
Academic Article Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity.
Academic Article Altered peptidase and viral-specific T cell response in LMP2 mutant mice.
Academic Article Role of proteasomes in antigen presentation.
Academic Article A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules.
Academic Article Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.
Academic Article A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation.
Academic Article A mutant antigen-presenting cell defective in antigen presentation expresses class II MHC molecules with an altered conformation.
Concept Antigen Presentation
Academic Article Substrate-induced protein stabilization reveals a predominant contribution from mature proteins to peptides presented on MHC class I.
Academic Article Re-examining class-I presentation and the DRiP hypothesis.
Academic Article Specialized proteasome subunits have an essential role in the thymic selection of CD8(+) T cells.
Academic Article Present Yourself! By MHC Class I and MHC Class II Molecules.
Academic Article Frequent Loss of IRF2 in Cancers Leads to Immune Evasion through Decreased MHC Class I Antigen Presentation and Increased PD-L1 Expression.
Academic Article The GTPase Rab39a promotes phagosome maturation into MHC-I antigen-presenting compartments.
Academic Article Cross-presentation of exogenous antigens on MHC I molecules.
Academic Article How a tailor achieves the perfect fit.
Academic Article Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation.
Academic Article Tetraspanin-5-mediated MHC class I clustering is required for optimal CD8 T cell activation.
Academic Article Pathways of MHC I cross-presentation of exogenous antigens.
Academic Article Tumor immune evasion through?loss of MHC class-I antigen presentation.
Search Criteria
  • Antigen Presentation