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Rheumatoid Arthritis (RA) is a chronic inflammatory disorder affecting 1% of the world population and results in the destruction of bone and joints. A two amino acid shared epitope LA 67,74 in HLA-DRB1 is highly associated with RA and is positively correlated with the level of anti-citrullinated protein antibodies. In contrast, a single amino acid shared epitope, D 70 in HLA-DRB1, is associated with resistance in a resistance dominance fashion. The HLA function in autoimmunity is unclear, but it is possible that citrullination of joint peptides increases their affinity to susceptible HLA molecules. In this study, we utilize a novel method for measuring HLA:peptide binding to answer this question. We measured binding of biotinylated citrullinated and native vimentin peptides to HLA molecules attached to Luminex beads; binding was detected with PE-streptavidin. Of the 91 HLA class II molecules, citrullinated vimentin bound over background on 88 of them. Citrullinated vimentin bound significantly more strongly than native vimentin to alleles with LA 67,74 (p = 0.0003). We observed no difference in binding between citrullinated and native vimentin peptides to alleles with D 70 [Fig. 1]. Citrullination of vimentin increased the peptide affinity for DRB1*LA 67,74 but not DRB1*D 70 . While native vimentin binds effectively to DRB1*D 70 , it does not bind well to DRB1*LA 67,74 . We also show peptides bind class II HLA (including alleles not associated with RA susceptibility or resistance) over a broad range, from very strong binding (MFI > 5000) to weaker binding (MFI ∼ 100). This demonstrates that HLA epitopes may mediate autoimmunity by preferentially binding autoantigens.