A SELF-REACTIVE CLASS I-RESTRICTED T-CELL RESPONSE OF H-2(B) 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 (CT L) response to determinants of the variable V beta 8.2 region of the b eta-chain of the T-cell receptor (TCR) for antigen in C57BL/6 (H-2(b)) mice. A CTL response was elicited in vivo by TCR peptide vaccination, and detected in vitro using syngeneic transfectants expressing a rear ranged V beta 8.2(+) TCR beta-chain. The first series of experiments u sed a 15-mer peptide representing residues 68-82 of the V beta 8.2 dom ain and containing K-b and D-b allele-specific motifs. Immunization wi th this peptide stimulated an autoreactive CTL response that cross-rea cted with V beta 8.2 epitopes presented by transfectants endogenously processing a V beta 8.2(+) TCR beta-chain. These transfectants express ed 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 subse t of peptide-primed mice was not deleted but its proliferative respons e to stimulation by the V beta 8.2-specific monoclonal antibody (mAb) F23.2 was suppressed. In a second series of experiments we immunized m ice with a 23-mer peptide representing residues 41-63 of the V beta 8. 2 domain that does not contain putative, allele-specific H-2(b) class I-restricted motifs. This TCR peptide vaccination stimulated a CD8(+) CTL response reacting against syngeneic, peptide-pulsed targets but no t 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 im munogenic peptide representing a naturally processed epitope of the V beta 8.2 domain of the TCR beta-chain induces a self-reactive CD8(+) C TL specific for this V beta 8.2 epitope; and anergizes (but does not d elete) V beta 8.2(+) T cells.