Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis.

Gerstner C, Dubnovitsky A, Sandin C, Kozhukh G, Uchtenhagen H, James EA, Rönnelid J, Ytterberg AJ, Pieper J, Reed E, Tandre K, Rieck M, Zubarev RA, Rönnblom L, Sandalova T, Buckner JH, Achour A, Malmström V

Front Immunol 7 (-) 494 [2016-11-14; online 2016-11-14]

Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLF

Affiliated researcher

PubMed 27895642

DOI 10.3389/fimmu.2016.00494

Crossref 10.3389/fimmu.2016.00494

pmc: PMC5108039