Thymic selection by a single MHC/peptide ligand produces a semidiverse repertoire of CD4+ T cells

Immunity. 1997 Aug;7(2):209-19. doi: 10.1016/s1074-7613(00)80524-5.


The influence of individual peptides in thymic selection was examined in H2-M- mice, in which positive selection is directed to a single peptide, class II-associated invariant chain peptide (CLIP) bound to H2-A(b). Two sensitive in vivo approaches showed that 70%-80% of CD4+ T cells undergoing positive selection to CLIP+H2-A(b) have self-reactivity to the various peptides expressed on wild-type H2-M+ antigen-presenting cells. When these self-reactive T cells were depleted, the residual CD4+ cells displayed a polyclonal repertoire in terms of alloreactivity, responses to foreign protein antigens, and Vbeta usage. Nevertheless, studies with two T cell receptor transgenic lines suggested that the repertoire of CD4+ cells induced by CLIP was less diverse than the repertoire of CD4+ cells in normal mice. Generation of a fully diverse T cell repertoire thus requires positive selection against multiple peptides.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • H-2 Antigens / metabolism*
  • Isoantigens / physiology
  • Ligands
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides / immunology*
  • Peptides / metabolism*
  • Radiation Chimera
  • Receptors, Antigen, T-Cell / genetics
  • Solubility
  • Stem Cells / immunology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • H-2 Antigens
  • Isoantigens
  • Ligands
  • Peptides
  • Receptors, Antigen, T-Cell