VACCINATION WITH T-CELL RECEPTOR PEPTIDES PRIMES ANTIRECEPTOR CYTOTOXIC T-LYMPHOCYTES (CTL) AND ANERGIZES T-CELLS SPECIFICALLY RECOGNIZED BY THESE CTL

We selected three peptides from the germ-line sequence of the V beta 8 .2 and J beta 2.3 gene segments of the murine T cell receptor for anti gen (TCR) which contained putative K-d- and L(d)-restricted epitopes. Immunization of BALB/c (H-2(d)) mice with the V beta 8.2(67-90) 23-mer peptide 1 as well as the 15-mer V beta 8.2(95-108)-peptide 2 efficien tly primed specific CD8(+) cytotoxic T lymphocyte (CTL) responses in v ivo against natural TCR-V beta 8.2 epitopes. V beta 8.2(+) T cells wer e not deleted in TCR peptide-immunized mice because the fractions of V beta 8.2(+) CD4(+) and V beta 8.2(+) CD8(+) T cells in spleen and lym ph nodes were not altered. The proliferative response of V beta 8.2(+) T cells to stimulation by monoclonal antibody F23.2 was selectively s uppressed (by 60-80%) in peptide-immunized BALB/c mice, indicating par tial anergy of this T subset. Immunization of BALB/c mice with the J b eta 2.3-derived peptide 3 stimulated a CD8(+) CTL response against a c lass I-restricted epitope within this J beta segment that was also gen erated during natural ''endogenous'' processing of this self antigen. These data confirm the predictive value of major histocompatibility co mplex class I allele-specific motifs. The described experiments indica te that TCR peptide-primed CD8(+) CTL recognize class I-restricted, na tural V beta/J beta-TCR epitopes. Such anti-TCR CTL may, thus, operate in V beta-specific immunoregulation of the T cell system suppressing their functional reactivity without deleting them.