T cell affinity maturation by selective expansion during infection

T lymphocyte recognition of infected cells is mediated by T cell receptors (TCRs) interacting with their ligands, self-major histocompatibility comple x (MHC) molecules complexed with pathogen-derived peptides. Serial TCR inte ractions with potentially small numbers of MHC/ peptide complexes on infect ed cells transmit signals that result in T lymphocyte expansion and activat ion of effector functions. The impact of TCR affinity for MHC/peptide compl exes on the rate or extent of in vivo T cell expansion is not known. Here w e show that in vivo expansion of complex T cell populations after bacterial infection is accompanied by an increase in their overall affinity for anti gen. T cell populations that have undergone additional rounds of in vivo ex pansion express a narrower range of TCRs, have increased sensitivity for an tigen in cytotoxic T lymphocyte assays, and bind MHC/peptide complexes with greater affinity. The selective expansion of higher affinity T cells provi des an in vivo mechanism for optimizing the early detection of infected cel ls.