The T cell repertoire primed by antiviral vaccination is influenced by self-tolerance.
Vaccination can elicit CD8(+) cytotoxic T lymphocytes (CTL) that recognize peptides presented by class I MHC molecules. Relatively little is known, however, about the genetic factors that shape the repertoire of T cell clonotypes responding to any given epitope. We report here that H-2(b) mice immunized with a plasmid DNA vaccine or vaccinia virus encoding for HIV-1SF2p55gag elicit CD8(+) CTL against the H-2Db-restricted immunodominant epitope (pgagb). This response involved three different T cell populations based on their recognition of alloantigens: one that cross-reacted with the alloantigen H-2Ld, one that cross-reacted with H-2Kd, and one that did not cross-react with either H-2(d) or H-2(k) molecules. Using the TAP-deficient cell line T2-Ld, we showed that pgagb-specific CTL cross-react with H-2Ld and a yet unidentified self-peptide. In mice expressing H-2(b) and H-2(d) allotypes, we investigated whether tolerance to H-2(d) influenced the HIVp55gag-specific CTL repertoire as a consequence of thymic deletion of the cross-reactive CTL repertoire. In (H-2(dxb))F1 mice heterogygosity at the MHC-I level prevented maturation of some but not all TCR combinations specific for H-2Db+pgagb, illustrating the concept that self-tolerance can influence the repertoire of antiviral T cells.
Paliard
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Chiron Corporation, 4560 Horton Street, Emeryville, California, 94608, USA.
Doe
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Walker
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D000818:Animals; D003429:Cross Reactions; D000939:Epitopes; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014765:Viral Vaccines / Q000494:pharmacology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D000939:Epitopes; D015683:Gene Products, gag; D010446:Peptide Fragments; D014765:Viral Vaccines; D054301:gag Gene Products, Human Immunodeficiency Virus; C109809:p2 gag peptide, Human immunodeficiency virus 1