Conservation of pathogenic TCR homology across class II restrictions in anti-ribonucleoprotein autoimmunity: extended efficacy of T cell vaccine therapy

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (9), p.4093-4102
• Main Authors: Zang, YunJuan, Martinez, Laisel, Fernandez, Irina, Pignac-Kobinger, Judith, Greidinger, Eric L
• Format: Article
• Language: English
• Subjects: Animals; Autoantigens - immunology; Autoimmune Diseases - immunology; Autoimmunity - immunology; Disease Models, Animal; Female; Histocompatibility Antigens Class II; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Receptors, Antigen, T-Cell - immunology; Ribonucleoproteins - immunology; T-Lymphocytes - immunology; Vaccines - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1203197

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.