Autoantigen BiP-Derived HLA-DR4 Epitopes Differentially Recognized by Effector and Regulatory T Cells in Rheumatoid Arthritis

Arthritis & Rheumatology
Hirofumi ShodaKazuhiko Yamamoto

Abstract

The balance between effector and regulatory CD4+ T cells plays a key role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine whether the RA autoantigen BiP has epitopes for both effector and regulatory immunities. The proliferation and cytokine secretion of peripheral blood mononuclear cells (PBMCs) from HLA-DR4-positive RA patients in response to BiP-derived peptides were examined by (3)H-thymidine uptake and enzyme-linked immunosorbent assay. As a mouse therapeutic model, a BiP-derived peptide was administered orally to mice with collagen-induced arthritis (CIA). Among the peptides examined, BiP(336-355) induced the strongest proliferation of PBMCs from RA patients, but not from healthy donors. The proliferation of PBMCs in response to BiP(336-355) showed a correlation with clinical RA activity and serum anti-BiP/citrullinated BiP antibodies. In contrast, BiP(456-475) induced interleukin-10 (IL-10) secretion from CD25-positive PBMCs obtained from RA patients and healthy donors without inducing cell proliferation, and it actively suppressed the BiP(336-355)-induced proliferation and proinflammatory cytokine secretion by PBMCs. Oral administration of BiP(456-475) to mice with CIA reduced the ...Continue Reading

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Citations

Mar 13, 2016·Autoimmunity Reviews·P ConigliaroR Perricone
Mar 18, 2015·Arthritis & Rheumatology·Laurie S Davis
Dec 3, 2016·Nature Reviews. Rheumatology·Fatemeh Navid, Robert A Colbert
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Apr 14, 2019·International Journal of Molecular Sciences·Kyeorda Kemp, Cody Poe
Apr 25, 2018·Trends in Pharmacological Sciences·Marveh RahmatiMichael F McDermott

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