A self-reactive class I-restricted T-cell response of H-2b mice to determinants of the V beta 8.2 domain of the T-cell receptor for antigen.

We studied the induction of a self-reactive cytotoxic T lymphocyte (CTL) response to determinants of the variable V beta 8.2 region of the beta-chain of the T-cell receptor (TCR) for antigen in C57BL/6 (H-2b) mice. A CTL response was elicited in vivo by TCR peptide vaccination, and detected in vitro using syngeneic transfectants expressing a rearranged V beta 8.2+ TCR beta-chain. The first series of experiments used a 15-mer peptide representing residues 68-82 of the V beta 8.2 domain and containing Kb and Db allele-specific motifs. Immunization with this peptide stimulated an autoreactive CTL response that cross-reacted with V beta 8.2 epitopes presented by transfectants endogenously processing a V beta 8.2+ TCR beta-chain. These transfectants expressed a construct derived from a murine, rearranged V beta 8.2/D beta 2/J beta 2.3/C beta 2 TCR beta-chain cDNA. The V beta 8.2+ T-cell subset of peptide-primed mice was not deleted but its proliferative response to stimulation by the V beta 8.2-specific monoclonal antibody (mAb) F23.2 was suppressed. In a second series of experiments we immunized mice with a 23-mer peptide representing residues 41-63 of the V beta 8.2 domain that does not contain putative, allele-specific H-2b class I-restricted motifs. This TCR peptide vaccination stimulated a CD8+ CTL response reacting against syngeneic, peptide-pulsed targets but not cross-reacting against transfectants processing/presenting epitopes of the beta-chain. V beta 8.2+ T cells of these peptide-primed mice were not anergized. These data demonstrate that vaccination with an immunogenic peptide representing a naturally processed epitope of the V beta 8.2 domain of the TCR beta-chain induces a self-reactive CD8+ CTL specific for this V beta 8.2 epitope; and anergizes (but does not delete) V beta 8.2+ T cells.