Thymic selection by a single MHC/peptide ligand produces a semidiverse repertoire of CD4+ T cells.
The influence of individual peptides in thymic selection was examined in H2-M- mice, in which positive selection is directed to a single peptide, class II-associated invariant chain peptide (CLIP) bound to H2-A(b). Two sensitive in vivo approaches showed that 70%-80% of CD4+ T cells undergoing positive selection to CLIP+H2-A(b) have self-reactivity to the various peptides expressed on wild-type H2-M+ antigen-presenting cells. When these self-reactive T cells were depleted, the residual CD4+ cells displayed a polyclonal repertoire in terms of alloreactivity, responses to foreign protein antigens, and Vbeta usage. Nevertheless, studies with two T cell receptor transgenic lines suggested that the repertoire of CD4+ cells induced by CLIP was less diverse than the repertoire of CD4+ cells in normal mice. Generation of a fully diverse T cell repertoire thus requires positive selection against multiple peptides.
Surh
C D
CD
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. csurh@scripps.edu
Lee
D S
DS
Fung-Leung
W P
WP
Karlsson
L
L
Sprent
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007519:Isoantigens / Q000502:physiology; D008024:Ligands; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012995:Solubility; D013234:Stem Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D006183:H-2 Antigens; D007519:Isoantigens; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell