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© The Rockefeller University Press, 0022-1007/1999/2/701/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 4, February 15, 1999 701-710

Articles

T Cell Affinity Maturation by Selective Expansion during Infection

Dirk H. Busch and Eric G. Pamer

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.

Key Words: cytotoxic T lymphocytes • Listeria monocytogenes • effector/memory/recall T cells • peptide sensitivity • affinity

Address correspondence to Eric G. Pamer, Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine, Laboratory of Clinical Investigation (LCI) 803, 333 Cedar St., New Haven, CT 06520. Phone: 203-785-3561; Fax: 203-785-3864; E-mail: eric.pamer{at}yale.edu

1 Abbreviations used in this paper: LLO, listeriolysin O; SA, streptavidin; SB, staining buffer.


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