Vaccination with T cell receptor peptides primes anti-receptor 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 antigen (TCR) which contained putative Kd- and Ld-restricted epitopes. Immunization of BALB/c (H-2d) 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 efficiently primed specific CD8+ cytotoxic T lymphocyte (CTL) responses in vivo against natural TCR-V beta 8.2 epitopes. V beta 8.2+ T cells were 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 lymph nodes were not altered. The proliferative response of V beta 8.2+ T cells to stimulation by monoclonal antibody F23.2 was selectively suppressed (by 60-80%) in peptide-immunized BALB/c mice, indicating partial anergy of this T subset. Immunization of BALB/c mice with the J beta 2.3-derived peptide 3 stimulated a CD8+ CTL response against a class I-restricted epitope within this J beta segment that was also generated during natural "endogenous" processing of this self antigen. These data confirm the predictive value of major histocompatibility complex class I allele-specific motifs. The described experiments indicate that TCR peptide-primed CD8+ CTL recognize class I-restricted, natural 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.
Kuhröber
A
A
Institute of Microbiology, University of Ulm, FRG.
Schirmbeck
R
R
Reimann
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017635:Clonal Anergy / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000939:Epitopes; D006183:H-2 Antigens; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta