Pathogen-Specific Inflammatory Milieux Tune the Antigen Sensitivity of CD8+ T Cells by Enhancing T Cell Receptor Signaling

Martin J. Richer, Jeffrey C. Nolz, John T. Harty

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)140-152
Number of pages13
JournalImmunity
Volume38
Issue number1
DOIs
StatePublished - Jan 24 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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