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 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.
Busch
D H
DH
Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
Pamer
E G
EG
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006460:Hemolysin Proteins; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*