title: 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.
abstract: 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-Abbeta0 mutation are highly susceptible to collagen-induced arthritis and describe the clinical course and histopathological changes in the affected joints.
authors.affiliation: Departments of Clinical Immunology, Rigshospitalet, 2200 N Copenhagen, Denmark.
authors.forename: E C
authors.initials: EC
authors.lastname: Andersson
authors.forename: B E
authors.initials: BE
authors.lastname: Hansen
authors.forename: H
authors.initials: H
authors.lastname: Jacobsen
authors.forename: L S
authors.initials: LS
authors.lastname: Madsen
authors.forename: C B
authors.initials: CB
authors.lastname: Andersen
authors.forename: J
authors.initials: J
authors.lastname: Engberg
authors.forename: J B
authors.initials: JB
authors.lastname: Rothbard
authors.forename: G S
authors.initials: GS
authors.lastname: McDevitt
authors.forename: V
authors.initials: V
authors.lastname: Malmström
authors.forename: R
authors.initials: R
authors.lastname: Holmdahl
authors.forename: A
authors.initials: A
authors.lastname: Svejgaard
authors.forename: L
authors.initials: L
authors.lastname: Fugger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell; D003094:Collagen