Abstract Text: While the CD4+ T cell response to citrullinated antigens has known importance in seropositive Rheumatoid Arthritis (RA), recognition of unmodified autoantigens and the phenotype of responding cells is not well characterized. By stimulating PBMC from DRB1*0401 RA patients with unmodified α-Enolase and Vimentin peptide libraries, we established a panel of DR restricted T cell lines with specificity toward six α-Enolase and two Vimentin peptides. These unmodified peptides were pooled and T cell reactivity to them was compared to a pool of previously published citrullinated epitopes in samples from patients with seropositive RA and age and sex matched controls through an ex vivo activation induced marker assay. RA individuals had both a 3 – fold greater antigen specific T cell response (mean 40.9 vs 13.5 specific T cells per 106 CD4+, respectively, p = 0.019), and a 3 – fold greater memory T cell response to the unmodified pool, vs controls (mean 11.0 vs 3.48 specific T cells per 106 CD4+, respectively, p = 0.0056). The magnitude of responses was similar to those elicited by the citrullinated peptide pool. Notably, in RA patients, the response to the unmodified peptides included a population of CXCR5+CXCR3-CCR6- T cells that was largely absent in controls (mean 1.60 vs 0.375 specific T cells per 106 CD4+, respectively, p =0.014). Our findings demonstrate that antigen specific T cells in seropositive RA patients also recognize non-citrullinated autoantigens, and these cells exhibit a peripheral TFH-like phenotype with known disease relevance.
