A. Kuhrober et al., 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, Immunology, 83(4), 1994, pp. 532-539
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.