Deficient positive selection of CD4 T cells in mice displaying altered repertoires of MHC class II-bound self-peptides

Immunity. 1997 Aug;7(2):197-208. doi: 10.1016/s1074-7613(00)80523-3.


The role of self-peptides in positive selection of CD4+ T cells has been controversial. We show that some self-peptides are presented by the MHC class II molecule I-A(b) in mice lacking Ii or H-2M but not in mice expressing a transgene-encoded peptide fused to I-A(b). In experiments using specific antibodies to block selection, these low-abundance self-peptides were implicated in the positive selection of some CD4+ T cells in H-2M-/- mice. However, all three mutant backgrounds failed to positively select two class II-restricted transgenic T cell receptors. Our findings suggest that minor components of the self-peptide repertoire can contribute to positive selection of a significant number of CD4+ T cells. In addition, the data suggest that T cell receptor repertoires selected in wild-type mice and in mice displaying limited spectra of self-peptides are distinct.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Epithelium / immunology
  • Epithelium / metabolism
  • Female
  • H-2 Antigens / genetics
  • H-2 Antigens / metabolism
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / metabolism*
  • Mice
  • Mice, Inbred A
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Peptides / genetics*
  • Peptides / immunology
  • Peptides / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Transgenes / immunology


  • H-2 Antigens
  • Histocompatibility Antigens Class II
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta