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 H-2D(b)-re-1(SF2)p55gag elicit CD8+ CTL against the H-2D(b)-restricted immunodominant epitope (pgag(b)). This response involved three different T cell populations based on their recognition of alloantigens: one that cross-reacted with the alloantigen H-2L(d), one that cross-reacted with H-2K(d), and one that did not crossreact with either H-2(d) or H-2(k) molecules. Using the TAP-deficient cell line T2-L-d, we showed that pgag(b)-specific CTL cross-react with H-2L(d) 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-2D(b) + pgag(b), illustrating the concept that self-tolerance can influence the repertoire of antiviral T cells. (C) 1998 Academic Press.