ORAL-ADMINISTRATION OF AN IMMUNODOMINANT HUMAN COLLAGEN PEPTIDE MODULATES COLLAGEN-INDUCED ARTHRITIS

Human type II collagen (HuCII) may be one of the autoantigens involved in human rheumatoid arthritis (RA). By using overlapping peptides, we have previously described an immunodominant region (HuCII.250-270) on HuCII. In the present study, this 21-mer HuCII.250-270 peptide was us ed as tolerogen, and its effect on both early and effector phase of co llagen-induced arthritis (CIA) was examined. Upon immunization with Hu CII-derived peptide 250-270, HuCII.250-270-tolerized mice showed dimin ished T cell proliferation that was mediated by Th1 cytokine, IL-2. Mo re interestingly, oral tolerance with HuCII.250-270 peptide also aboli shed anti-human and anti-mouse (autoantibody) CII Ab. Ab isotype data also showed that oral administration of HuCII.250-270 peptide diminish es primarily a Th1 type of immune response. Arthritis severity was red uced markedly in mice orally tolerized with HuCII.250-270 peptide both at early and effector phases. Suppression of CIA at the effector phas e by oral administration of HuCII peptide suggests a potential immunot herapeutic use of collagen II peptide in the treatment of human RA.