Characterization of murine T cell responses to peptides of the variable region of self T cell receptor beta-chains.
Immunization with peptides of the TCR may regulate cellular immune responses that are dominated by a particular TCR. However, no extensive study of the immunogenicity of peptides of different regions of the V beta chain of the TCR has been done. We have tested the immunogenicity of several V beta peptides in several strains of mice and characterized the cellular response to these peptides. We examined the ability of six strains of mice of H-2b, H-2d, or H-2k and of mouse lymphocyte stimulatory (Mls)-1a or Mls-1b haplotypes to respond to several peptides of the V beta 6 region and an NH2-terminal peptide of other V beta of the TCR. These include V beta 6 peptides 1-20, 32-48, 39-60, 48-75, 58-75, and V beta 3, V beta 8.1, and V beta 8.3 peptides 1-20. The various mouse strains respond to these peptides independently of deletion of V beta 6+ T cells from peripheral lymphocytes. All of the Mls deleting and nondeleting strains tested respond weakly to one peptide of V beta 6, V beta 6(39-60). Antibody titers were also demonstrated in BALB/c and DBA/2J to V beta 6(1-20), V beta 6(39-60) and V beta 6(48-75), but not to V beta 6(32-48). We demonstrated that T cells responding to V beta 6(32-48) produce IL-2 and IFN-gamma, consistent with the Th1 subset of T cells. None of the antipeptide antibodies recognized the intact V beta 6 TCR on the cell surface. In vitro antibody blocking studies with TCR peptides show that these peptides are presented by class II MHC to CD4+ T cells. We conclude that the T cell and B cell repertoires contain cells able to respond to peptides of self TCR and immunization with peptides induces CD4+ T cells and that these cells may have an immunoregulatory role.
MacNeil
D
D
Department of Immunology, University of Alberta, Edmonton, Canada.
Fraga
E
E
Singh
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta