T cell affinity maturation by selective expansion during infection

Dirk H. Busch, Eric G. Pamer

Research output: Contribution to journalArticlepeer-review

357 Scopus citations

Abstract

T lymphocyte recognition of infected cells is mediated by T cell receptors (TCRs) interacting with their ligands, self-major histocompatibility complex (MHC) molecules complexed with pathogen-derived peptides. Serial TCR interactions with potentially small numbers of MHC/peptide complexes on infected cells transmit signals that result in T lymphocyte expansion and activation of effector functions. The impact of TCR affinity for MHC/peptide complexes on the rate or extent of in vivo T cell expansion is not known. Here we show that in vivo expansion of complex T cell populations after bacterial infection is accompanied by an increase in their overall affinity for antigen. T cell populations that have undergone additional rounds of in vivo expansion express a narrower range of TCRs, have increased sensitivity for antigen in cytotoxic T lymphocyte assays, and bind MHC/peptide complexes with greater affinity. The selective expansion of higher affinity T cells provides an in vivo mechanism for optimizing the early detection of infected cells.

Original languageEnglish
Pages (from-to)701-709
Number of pages9
JournalJournal of Experimental Medicine
Volume189
Issue number4
DOIs
StatePublished - 15 Feb 1999
Externally publishedYes

Keywords

  • Affinity
  • Cytotoxic T lymphocytes
  • Effector/memory/recall T cells
  • Listeria monocytogenes
  • Peptide sensitivity

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