Pathogen-specific inflammatory milieux tune the antigen sensitivity of CD8(+) T cells by enhancing T cell receptor signaling

Immunity. 2013 Jan 24;38(1):140-52. doi: 10.1016/j.immuni.2012.09.017. Epub 2012 Dec 20.


CD8(+) T cells confer host protection through T-cell-receptor (TCR)-mediated recognition of foreign antigens presented by infected cells. Thus, generation of CD8(+) T cell populations with high antigen sensitivity is critical for efficient pathogen clearance. Besides selection of high-affinity TCRs, the molecular mechanisms regulating the antigen sensitivity of CD8(+) T cells remain poorly defined. Herein, we have demonstrated that the antigen sensitivity of effector and memory CD8(+) T cells is dynamically regulated and can be tuned by pathogen-induced inflammatory milieux independently of the selection of cells with higher TCR affinity. Mechanistically, we have demonstrated that the signal-transduction capacity of key TCR proximal molecules is enhanced by inflammatory cytokines, which reduced the antigen density required to trigger antimicrobial functions. Dynamic tuning of CD8(+) T cell antigen sensitivity by inflammatory cytokines most likely optimizes immunity to specific pathogens while minimizing the risk of immunopathology at steady state.

Publication types

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

MeSH terms

  • Animals
  • Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Clonal Selection, Antigen-Mediated
  • Cytokines / immunology
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte
  • Immunologic Memory
  • Inflammation / immunology*
  • Inflammation / metabolism*
  • Inflammation Mediators / immunology
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*


  • Antigens
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Inflammation Mediators
  • Receptors, Antigen, T-Cell