A kinetic basis for T cell receptor repertoire selection during an immune response.
The basis for T cell antigen receptor (TCR) repertoire selection upon repeated antigenic challenge is unclear. We evaluated the avidity and dissociation kinetics of peptide/major histocompatibility complex (MHC) tetramer binding to antigen-specific T lymphocytes isolated following primary or secondary immunization. The data reveal a narrowing of the secondary repertoire relative to the primary repertoire, largely resulting from the loss of cells expressing TCRs with the fastest dissociation rates for peptide/MHC binding. In addition, T cells in the secondary response express TCRs of higher average affinity for peptide/MHC than cells in the primary response. These results provide a link between the kinetics and affinity of TCR-peptide/MHC interactions and TCR sequence selection during the course of an immune response.
Savage
P A
PA
Program in Cancer Biology, Stanford University School of Medicine, California 94305, USA.
Boniface
J J
JJ
Davis
M M
MM
D000818:Animals; D001665:Binding Sites / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000378:metabolism
D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell