Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion

Immunity. 2000 Dec;13(6):829-40. doi: 10.1016/s1074-7613(00)00080-7.

Abstract

How negative selection shapes a polyclonal population of self-reactive T cells has been difficult to address directly because of the lack of means to isolate T cells reactive to a particular self-peptide. Here, using mice transgenic for the TCR-beta chain of a CTL clone directed against a male-specific peptide, we compared the preimmune repertoire reactive to this peptide in male and female animals. Surprisingly, in the presence of the deleting ligand, as many as 25%-40% of reactive T cells escaped clonal deletion. A correlation was found between T cell avidity, TCRalpha structures, and susceptibility to negative selection. These results suggest that numerous low-affinity self-specific T cells persist in the periphery and show that a deleting ligand can specifically narrow the structural diversity of the TCR repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / immunology*
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology*
  • Clone Cells
  • DNA, Complementary
  • Female
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Immunophenotyping
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptides / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*

Substances

  • Autoantigens
  • DNA, Complementary
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta