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 used as tolerogen, and its effect on both early and effector phase of collagen-induced arthritis (CIA) was examined. Upon immunization with HuCII-derived peptide 250-270, HuCII.250-270-tolerized mice showed diminished T cell proliferation that was mediated by Th1 cytokine, IL-2. More interestingly, oral tolerance with Hu- CII.250-270 peptide also abolished anti-human and anti-mouse (autoantibody) CII Ab. Ab isotype data also showed that oral administration of HuCII.250- 270 peptide diminishes primarily a Th1 type of immune response. Arthritis severity was reduced markedly in mice orally tolerized with HuCII.250-270 peptide both at early and effector phases. Suppression of CIA at the effector phase by oral administration of HuCII peptide suggests a potential immunotherapeutic use of collagen II peptide in the treatment of human RA.