Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes

Immunity. 1997 Aug;7(2):221-31. doi: 10.1016/s1074-7613(00)80525-7.

Abstract

To understand how thymic selection gives rise to T cells that are capable of major histocompatibility complex (MHC)-restricted recognition of antigen but are tolerant of self, we directly examined how peptide/MHC ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. We demonstrate that abundant self-peptides, purified from the H-2D(b) molecules of thymic epithelial cells, are specifically recognized during the positive selection of CD8+ T cells, implying that positive selection generates a repertoire of T cells that is weakly self-reactive. We also found that this recognition is somewhat cross-reactive, thereby providing an explanation for how the specific recognition of a limited repertoire of thymic self-peptides can select a diverse repertoire of T cells.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • Autoantigens / isolation & purification
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cell Line
  • Cytotoxicity, Immunologic
  • Epithelium / immunology
  • Female
  • Fetus
  • Lymphocyte Activation*
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Organ Culture Techniques
  • Peptide Fragments / immunology*
  • Peptide Fragments / isolation & purification
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / virology
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Autoantigens
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta