Requirement for diverse, low-abundance peptides in positive selection of T cells

Science. 1999 Jan 1;283(5398):67-70. doi: 10.1126/science.283.5398.67.

Abstract

Whether a single major histocompatibility complex (MHC)-bound peptide can drive the positive selection of large numbers of T cells has been a controversial issue. A diverse population of self peptides was shown to be essential for the in vivo development of CD4 T cells. Mice in which all but 5 percent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent was lost, CD4 T cell development was impaired. Blocking the major peptide-MHC complex in thymus organ culture had no effect on T cell development, indicating that positive selection occurred on the diverse peptides present at low levels. This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Peptides / immunology*
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / metabolism
  • Spleen / immunology
  • Thymus Gland / immunology

Substances

  • Histocompatibility Antigens Class II
  • Peptides
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins