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
| Autor: | Lars Fugger, Claus B. Andersen, Rikard Holmdahl, Ellen Christina Andersson, Vivianne Malmström, Helle Jacobsen, Lars S. Madsen, Jonathan B. Rothbard, Bjarke E. Hansen, Grete Sonderstrup McDevitt, Arne Svejgaard, Jan Engberg |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
musculoskeletal diseases
CD4-Positive T-Lymphocytes T cell Molecular Sequence Data Type II collagen Receptors Antigen T-Cell Arthritis Peptide binding chemical and pharmacologic phenomena Mice Transgenic Human leukocyte antigen Biology Major histocompatibility complex Epitope Arthritis Rheumatoid Mice Antigen immune system diseases Antibody Specificity medicine HLA-DR4 Antigen Animals Humans Amino Acid Sequence skin and connective tissue diseases Multidisciplinary Binding Sites Immunodominant Epitopes HLA-DR Antigens Biological Sciences medicine.disease Molecular biology medicine.anatomical_structure Immunology biology.protein Collagen HLA-DRB1 Chains |
| Popis: | 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-Abβ0mutation are highly susceptible to collagen-induced arthritis and describe the clinical course and histopathological changes in the affected joints. |
| Databáze: | OpenAIRE |
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