title: Conservation of pathogenic TCR homology across class II restrictions in anti-ribonucleoprotein autoimmunity: extended efficacy of T cell vaccine therapy.
abstract: T cells have been shown to mediate aspects of anti-ribonucleoprotein (RNP) autoimmunity, and are a potential target of therapy in lupus and related diseases. In this study, we assessed the relevance of a conserved class of anti-RNP T cells to autoimmune disease expression and therapy. Our data show that anti-RNP T cell selection induced a limited set of homologous CDR3 motifs at high frequency. Homologous CDR3 motifs have been reported in other autoimmune diseases. Vaccination with irradiated anti-RNP (but not anti-tetanus toxoid) CD4(+) cells induced remission of anti-RNP-associated nephritis in ≥ 80% of treated mice, even with donor/recipient MHC class II mismatch, and in both induced and spontaneous autoimmunity. Vaccine responder sera inhibited anti-70k T cell proliferation and bound hybridomas expressing the conserved CDR3 motifs. Our data indicate that a limited set of TCR CDR3 motifs may be important for the pathogenesis of anti-RNP lupus and other autoimmune diseases. The ability to target a consistent set of pathogenic T cells between individuals and across class II restrictions may allow for the more practical development of a standardized anti-RNP T cell vaccine preparation useful for multiple patients.
authors.affiliation: Division of Rheumatology, University of Miami Miller School of Medicine, Miami, FL 33136;
authors.forename: YunJuan
authors.initials: Y
authors.lastname: Zang
authors.forename: Laisel
authors.initials: L
authors.lastname: Martinez
authors.forename: Irina
authors.initials: I
authors.lastname: Fernandez
authors.forename: Judith
authors.initials: J
authors.lastname: Pignac-Kobinger
authors.forename: Eric L
authors.initials: EL
authors.lastname: Greidinger
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D012261:Ribonucleoproteins; D014612:Vaccines