Thymic selection generates a large T cell pool recognizing a self-peptide in humans

J Exp Med. 2002 Feb 18;195(4):485-94. doi: 10.1084/jem.20011658.

Abstract

The low frequency of self-peptide-specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single-positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1-specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide-specific T cell repertoire directly accessible in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm
  • Autoantigens / immunology*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Flow Cytometry
  • Gene Rearrangement, T-Lymphocyte / genetics
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunologic Memory
  • Infant, Newborn
  • Lymphocyte Activation
  • MART-1 Antigen
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Stem Cells / cytology
  • Stem Cells / immunology
  • Telomere / genetics
  • Thymus Gland / cytology*
  • Thymus Gland / immunology*

Substances

  • Antigens, Neoplasm
  • Autoantigens
  • HLA-A2 Antigen
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta