Characteristics of T Cell Receptors View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

1982-2019

FUNDING AMOUNT

5224995 USD

ABSTRACT

DESCRIPTION (provided by applicant): T cells bearing ?? T cell receptors (TCRs) are responsible for driving specific immune responses against invading organisms and, in the case of autoimmunity, against self. The TCRs on these cells react with antigenic peptides bound to major histocompatibility complex proteins (MHC). The reasons for the bias of TCRs for interaction with MHC has long been debated, however, recent evidence suggests that evolution has selected for amino acids at certain positions on TCRs that have a built in likelihood of engaging MHC. This project will investigate the nature of the sites on MHC that are the reciprocal of those on TCRs i.e. that consistently engage the evolutionarily selected MHC-reacting amino acids of TCRs. Although evidence suggests that TCRs have the ability to react generically with MHC, individual TCRs are certainly specific for particular types and alleles of MHC proteins, as witnessed by the MHC allele restriction conferred on T cells during positive selection in the thymus. This project will study the structural bases for MHC allele specificity on the part of T cells. Regulatory T cells prevent immune responses against certain tissues in the body. It is thought that they do this by reacting with MHC bound to self-peptides that are present in the tissue at issue. In spite of much work, little is known about the endogenous peptides that are recognized in normal mice by endogenous regulatory T cells. Mice and methods developed in this Project will be used, in conjunction with MHC/peptide libraries, to identify self-peptides that are recognized by regulatory T cells. Overall, this Project will investigate various aspects o the TCR/MHC/peptide interaction. It will thus provide a firmer basis for our understanding of the structural bases for TCR interaction with generic and particular MHC proteins and illuminate the long mysterious process of T cell positive selection. Studies will also establish the nature of sel-peptides recognized in association with MHC by regulatory T cells, a discovery which will help understanding of the mode of action of regulatory T cells and perhaps improve ability to manipulate these cells in vivo. More... »

URL

http://projectreporter.nih.gov/project_info_description.cfm?aid=9480035

Related SciGraph Publications

  • 2018-12. TCR signal strength controls thymic differentiation of iNKT cell subsets in NATURE COMMUNICATIONS
  • 2018-12. Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7 in SCIENTIFIC REPORTS
  • 2014-07. Molecules in medicine mini review: the αβ T cell receptor in JOURNAL OF MOLECULAR MEDICINE
  • 2014-04. Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice in GENES & IMMUNITY
  • 2013-03. TLR7 drives accumulation of ABCs and autoantibody production in autoimmune-prone mice in IMMUNOLOGIC RESEARCH
  • 2013-01. Recognition of self and altered self by T cells in autoimmunity and allergy in PROTEIN & CELL
  • 2010-03. Chromogranin A is an autoantigen in type 1 diabetes in NATURE IMMUNOLOGY
  • 2009-04. Germline-encoded amino acids in the αβ T-cell receptor control thymic selection in NATURE
  • 2008-09. GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth in CELL RESEARCH
  • 2007-10. Germline-encoded recognition of diverse glycolipids by natural killer T cells in NATURE IMMUNOLOGY
  • 2007-03. Elucidation of some Bax conformational changes through crystallization of an antibody–peptide complex in CELL DEATH & DIFFERENTIATION
  • 2006-11. Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide in NATURE IMMUNOLOGY
  • 2003-10. Mast cell–dependent migration of effector CD8+ T cells through production of leukotriene B4 in NATURE IMMUNOLOGY
  • 2002-05. Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2 in GENES & IMMUNITY
  • 2002. Some Properties of T Cells in Animals in LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION IX
  • 2002-01. T cells down-modulate peptide-MHC complexes on APCs in vivo in NATURE IMMUNOLOGY
  • 2001-08. Autoimmune disease: why and where it occurs in NATURE MEDICINE
  • 2001-05. Immunological adjuvants promote activated T cell survival via induction of Bcl-3 in NATURE IMMUNOLOGY
  • 1988-12. Development of T cell receptor expression: Studies using T cell hybridomas in IMMUNOLOGIC RESEARCH
  • 1987. The T Cell Receptor: Its Repertoire and Role in Thymocyte Development in MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION
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