Conservation of Pathogenic TCR Homology across Class II Restrictions in Anti-Ribonucleoprotein Autoimmunity: Extended Efficacy of T Cell Vaccine Therapy
| Autor: | Laisel Martinez, Judith Pignac-Kobinger, Yunjuan Zang, Eric L. Greidinger, Irina Fernandez |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:4093-4102 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1203197 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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