Definition of MHC and T cell receptor contacts in the HLA-DR4-restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice
Definition of MHC and T cell receptor contacts in the HLA-DR4-restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice
复制标题
DOI：
10.1073/pnas.95.13.7574
复制
发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Fugger, L
中科院分区：
文献类型：
--
作者：
Andersson, EC;Hansen, BE;Fugger, L
类风湿性关节炎（RA）是一种与HLA-DR 4和DR 1等位基因相关的自身免疫性疾病。RA中的靶自身抗原是未知的，但II型胶原（CII）是候选抗原，并且该蛋白中的DR 4-和DR 1-限制性免疫显性T细胞表位对应于氨基酸261-273（Cn 261-273）。我们已经定义了CII 261-273中的MHC和T细胞受体接触，并提供了强有力的证据表明，该肽对应于先前发现的RA相关DR分子的肽结合特异性。此外，我们证明了HLA-DR 4和人CD 4转基因小鼠I-A（β）（B）（0）突变纯合子对胶原诱导的关节炎高度易感，并描述了受累关节的临床病程和组织病理学变化。
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 (Cn 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(beta)(b)(0) mutation are highly susceptible to collagen-induced arthritis and describe the clinical course and histopathological changes in the affected joints.