T Cell-Positive Selection Uses Self-Ligand Binding Strength to Optimize Repertoire Recognition of Foreign Antigens

Immunity. 2013 Feb 21;38(2):263-274. doi: 10.1016/j.immuni.2012.09.011. Epub 2013 Jan 3.

Abstract

Developing T cells express diverse antigen receptors whose specificities are not prematched to the foreign antigens they eventually encounter. Past experiments have revealed that thymocytes must productively signal in response to self antigens to mature and enter the peripheral T cell pool (positive selection), but how this process enhances effective mature T cell responses to foreign antigen is not fully understood. Here we have documented an unsuspected connection between thymic recognition events and foreign antigen-driven T cell responses. We find that the strength of self-reactivity is a clone-specific property unexpectedly directly related to the strength of T cell receptor (TCR) binding to presented foreign antigen. T cells with receptors showing stronger interaction with self dominate in responses to infections and accumulate in aging individuals, revealing that positive selection contributes to effective immunity by skewing the mature TCR repertoire toward highly effective recognition of pathogens that pose a danger to the host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adoptive Transfer
  • Aging / genetics
  • Aging / immunology*
  • Animals
  • Antigens, Bacterial / immunology*
  • Antigens, Viral / immunology*
  • Autoantigens / genetics
  • Autoantigens / immunology
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology
  • CD5 Antigens / genetics
  • CD5 Antigens / immunology
  • Cell Differentiation
  • Humans
  • Hybridomas / immunology
  • Listeria monocytogenes / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / microbiology
  • Lymph Nodes / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Selection, Genetic / immunology
  • Spleen / immunology
  • Spleen / microbiology
  • Spleen / virology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / microbiology
  • T-Lymphocytes / transplantation
  • T-Lymphocytes / virology

Substances

  • Antigens, Bacterial
  • Antigens, Viral
  • Autoantigens
  • CD4 Antigens
  • CD5 Antigens
  • Receptors, Antigen, T-Cell