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Definition of MHC and T cell receptor contacts in the HLA-DR4restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice

1998; National Academy of Sciences; Volume: 95; Issue: 13 Linguagem: Inglês

10.1073/pnas.95.13.7574

1091-6490

Ellen Andersson, Bjarke Endel Hansen, Helle J. Jacobsen, Lars Siim Madsen, Claus B. Andersen, Jan Engberg, Jonathan B. Rothbard, Grete Sønderstrup McDevitt, Vivianne Malmström, Rikard Holmdahl, Arne Svejgaard, Lars Fugger,

Immunotherapy and Immune Responses

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