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-2bmice 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-2dor H-2kmolecules. Using the TAP-deficient cell line T2-Ld, we showed that pgagb-specific CTL cross-react with H-2Ldand a yet unidentified self-peptide. In mice expressing H-2band H-2dallotypes, we investigated whether tolerance to H-2dinfluenced the HIVp55gag-specific CTL repertoire as a consequence of thymic deletion of the cross-reactive CTL repertoire. In (H-2dxb)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.