How the T cell repertoire becomes peptide and MHC specific

Cell. 2005 Jul 29;122(2):247-60. doi: 10.1016/j.cell.2005.05.013.

Abstract

T cells bearing alphabeta T cell receptors (TCRs) recognize antigens in the form of peptides bound to class I or class II major histocompatibility proteins (MHC). TCRs on mature T cells are usually very specific for both peptide and MHC class and allele. They are picked out from a precursor population in the thymus by MHC-driven positive and negative selection. Here we show that the pool of T cells initially positively selected in the thymus contains many T cells that are very crossreactive for peptide and MHC and that subsequent negative selection establishes the MHC-restriction and peptide specificity of peripheral T cells. Our results also suggest that germline-encoded TCR variable elements have an inherent predisposition to react with features shared by all MHC proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Germ-Line Mutation
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Hybridomas / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Immunological
  • Models, Molecular
  • Peptides / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta