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

Yunjuan Zang, Laisel Martinez, Irina Fernandez, Judith Pignac-Kobinger, Eric L. Greidinger

Research output: Contribution to journalArticle

7 Scopus citations

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. The Journal of Immunology, 2014, 192: 4093-4102.

Original languageEnglish (US)
Pages (from-to)4093-4102
Number of pages10
JournalJournal of Immunology
Volume192
Issue number9
DOIs
StatePublished - May 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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