Immunological function of a defined T-cell population tolerized to low-affinity self antigens

Nature. 1995 Mar 2;374(6517):68-9. doi: 10.1038/374068a0.


In the thymus there are two major mechanisms of T-lymphocyte tolerance: clonal deletion and clonal inactivation. One important problem underlying the mechanism of clonal inactivation is why unresponsive cells are maintained in the mature peripheral T-cell repertoire. Here we report that transgenic alpha beta T-cells may be tolerized to a self antigen Mls-1a, but still retain proliferative responses for alternative peptide antigens and superantigens. These self-tolerant T cells can also provide immunopathological and memory cytotoxic function in vivo. We propose that high-affinity/avidity self-reactive T cells are deleted in the thymus, whereas lower-affinity/avidity interactions lead to unresponsiveness and define the 'resting threshold' for a given T cell. These low-affinity self-tolerant T cells remain functionally competent for high-affinity foreign antigens, and efficiently eliminate natural pathogens in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • Cell Differentiation
  • Clonal Anergy
  • Enterotoxins / immunology
  • H-2 Antigens / immunology
  • In Vitro Techniques
  • Lymphocyte Activation
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Minor Lymphocyte Stimulatory Antigens / immunology
  • Rats
  • Self Tolerance*
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology


  • Autoantigens
  • Enterotoxins
  • H-2 Antigens
  • Minor Lymphocyte Stimulatory Antigens
  • enterotoxin B, staphylococcal