A. Kuhrober et al., VACCINATION WITH T-CELL RECEPTOR PEPTIDES PRIMES ANTIRECEPTOR CYTOTOXIC T-LYMPHOCYTES (CTL) AND ANERGIZES T-CELLS SPECIFICALLY RECOGNIZED BY THESE CTL, European Journal of Immunology, 24(5), 1994, pp. 1172-1180
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.