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J. Exp. Med.,
Volume 189, Number 4, February 15, 1999 701-710
By
From the Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine,
New Haven, Connecticut 06511
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.
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