DEFINITION OF MHC AND T-CELL RECEPTOR CONTACTS IN THE HLA-DR4-RESTRICTED IMMUNODOMINANT EPITOPE IN TYPE-II COLLAGEN AND CHARACTERIZATION OFCOLLAGEN-INDUCED ARTHRITIS IN HLA-DR4 AND HUMAN CD4 TRANSGENIC MICE

Rheumatoid arthritis (RA) is an autoimmune disease associated with the HLA-DR4 and DR1 alleles. The target autoantigen(s) in RA is unknown b ut type II collagen (CII) is a candidate, and the DR4- and DR1-restric ted immunodominant T cell epitope in this protein corresponds to amino acids 261-273 (Cn 261-273). We have defined MHC and T cell receptor c ontacts in CII 261-273 and provide strong evidence that this peptide c orresponds to the peptide binding specificity previously found for RA- associated DR molecules. Moreover, we demonstrate that HLA-DR4 and hum an CD4 transgenic mice homozygous for the I-A(beta)(b)(0) mutation are highly susceptible to collagen-induced arthritis and describe the cli nical course and histopathological changes in the affected joints.