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Biography

Eric S. Huseby received his B.S. in Chemical Engineering (1992) and Ph.D. in Immunology (2000) from the University of Washington. He was a Howard Hughes Medical Institute post doctoral fellow at the National Jewish Medical Center. He joined the Department of Pathology at the University of Massachusetts as a faculty member in September of 2006 and is a 2007 Arnold and Mabel Beckman Young Investigator and a 2008 Searle Scholar.

Development of T cell tolerance of self and the autoimmune consequence of when it fails.

Dr. Eric Huseby

My lab is focused on the molecular and cellular pathways that govern the generation, maintenance and function of a self tolerant T cell repertoire and the autoimmune consequences of when self tolerance fails. To understand how T cell repertoires develop and how defects in the process lead to autoimmune disease, we are studying three major aspects of T cell function.

1) How does the specificity of the TCR for MHC + peptides (pMHC) effect T cell development and drive T cell function?

The ability of T cells to distinguish highly similar peptide ligands bound to a specific class of MHC proteins (pMHC) is the underlying basis for a functioning adaptive immune system. Failures in purging self-reactive TCRs underlie the predisposition to autoimmune disease. To understand why self-reactive T cells are generated and how they recognize pMHC ligands, we have created a series of analytic methods to probe TCR-pMHC binding. The methods we are generating use high-throughput pMHC display libraries to decipher how T cells interact with their pMHC ligands. These novel display libraries will be used to decipher how positive and negative selection shapes the T cell repertoire and to evaluate how TCR cross-reactivity for pMHC ligands influences which T cells enter an immune response.

2) How does the affinity and binding kinetics of TCR – pMHC interactions impact mature T cell activation and memory T cell formation?

Mature T cells undergo rapid differentiation into effector and memory T cells when challenged with high affinity pathogen derived ligands. To study how mature T cells discriminate between different affinity ligands, we have created a series of viruses that express biophysically defined T cell ligands for CD4 T cells. Using these recombinant viruses and corresponding CD4 T cells, we are determining when, where and how T cells determine to enter into the immune response.

3) Why do some self-reactive T cells escape tolerance induction and when activated, induce autoimmunity?

Although thymic deletion purges most T cells with reactivity for self proteins, autoimmune diseases clearly demonstrate that T cell tolerance of self is incomplete. Many studies have indicated that everyone harbors T cells reactive to self proteins, however only a fraction of people succumb to autoimmune disease. Thus not all self reactive T cell repertoires are pathogenic. Using a T cell mediated model of the autoimmune disease, we are determining whether there is a T cell intrinsic difference in self-reactive, pathogenic versus non-pathogenic T cell repertoires or whether all self reactive T cell repertoires have the capability to pathogenic and autoimmunity is predominately a reaction to a specific triggering event.

Rotation Projects

Rotations

Potential rotations

1. To examine how TCR affinity and specificity for MHC + peptide influences the development and activation of CD4 T cells.

2. To assess the impact of self tolerance on the specificity, affinity and pathogenic potential of T cells reactive to proteins expressed in the central nervous system and b-islet cells of the pancreas.

One or more keywords matched the following items that are connected to Huseby, Eric
Item TypeName
Academic Article Thymic stromal organization is regulated by the specificity of T cell receptor/major histocompatibility complex interactions.
Academic Article Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines.
Academic Article Highly cross-reactive T cell responses to myelin basic protein epitopes reveal a nonpredictable form of TCR degeneracy.
Academic Article Age-dependent T cell tolerance and autoimmunity to myelin basic protein.
Academic Article CD8(+) T cell tolerance to a tumor-associated antigen is maintained at the level of expansion rather than effector function.
Academic Article Mimotopes for alloreactive and conventional T cells in a peptide-MHC display library.
Academic Article Cutting edge: myelin basic protein-specific cytotoxic T cell tolerance is maintained in vivo by a single dominant epitope in H-2k mice.
Academic Article The role of CD8(+) T cells in multiple sclerosis and its animal models.
Academic Article How the T cell repertoire becomes peptide and MHC specific.
Academic Article Tolerating the nervous system: a delicate balance.
Academic Article Dendritic cells lose ability to present protein antigen after stimulating antigen-specific T cell responses, despite upregulation of MHC class II expression.
Academic Article Regulatory T cells maintain long-term tolerance to myelin basic protein by inducing a novel, dynamic state of T cell tolerance.
Academic Article IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state.
Academic Article Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor.
Academic Article A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis.
Academic Article Fast on-rates allow short dwell time ligands to activate T cells.
Academic Article A single T cell receptor bound to major histocompatibility complex class I and class II glycoproteins reveals switchable TCR conformers.
Academic Article A role for differential variable gene pairing in creating T cell receptors specific for unique major histocompatibility ligands.
Academic Article Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection.
Academic Article Negative selection imparts peptide specificity to the mature T cell repertoire.
Academic Article Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide.
Academic Article Thymic selection stifles TCR reactivity with the main chain structure of MHC and forces interactions with the peptide side chains.
Academic Article Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules.
Academic Article How the thymus designs antigen-specific and self-tolerant T cell receptor sequences.
Academic Article Ligand mobility modulates immunological synapse formation and T cell activation.
Academic Article Single naive CD4+ T cells from a diverse repertoire produce different effector cell types during infection.
Concept T-Lymphocytes, Cytotoxic
Concept T-Cell Antigen Receptor Specificity
Concept CD8-Positive T-Lymphocytes
Concept T-Lymphocytes, Helper-Inducer
Concept T-Lymphocytes, Regulatory
Concept T-Lymphocyte Subsets
Concept Epitopes, T-Lymphocyte
Concept ZAP-70 Protein-Tyrosine Kinase
Concept T-Lymphocytes
Concept Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Concept Lymphocyte Activation
Concept CD4-Positive T-Lymphocytes
Concept B-Lymphocytes
Concept Lymphocyte Transfusion
Academic Article Relapsing-remitting central nervous system autoimmunity mediated by GFAP-specific CD8 T cells.
Academic Article Identifying environmental antigens that activate myelin-specific T cells.
Academic Article Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity.
Academic Article Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.
Academic Article Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance.
Academic Article ?? T cell receptors as predictors of health and disease.
Academic Article Indoctrinating T cells to attack pathogens through homeschooling.
Academic Article A "hotspot" for autoimmune T cells in type 1 diabetes.
Academic Article Hydrophobic CDR3 residues promote the development of self-reactive T cells.
Academic Article Affinity for self antigen selects Treg cells with distinct functional properties.
Academic Article Abnormalities of T-cell receptor repertoire in CD4+ regulatory and conventional T cells in patients with RAG mutations: Implications for autoimmunity.
Academic Article Patients with CD3G mutations reveal a role for human CD3? in Treg diversity and suppressive function.
Academic Article Killer T cells with a beta-flavi(r) for dengue.
Academic Article A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3+ Treg cell development.
Academic Article Neonatal-derived IL-17 producing dermal ?? T cells are required to prevent spontaneous atopic dermatitis.
Academic Article How to Prevent yourself from Seeing Double.
Academic Article Resolving the Instructions for ?? T Cell Development.
Academic Article The perception and response of T cells to a changing environment are based on the law of initial value.
Search Criteria
  • Lymphocyte
  • Specific
  • Protein Tyrosine Kinase
  • p56 lck