II型胶原蛋白中HLA - DR4限制性免疫显性表位的MHC与T细胞受体接触的定义以及HLA - DR4和人CD4转基因小鼠中胶原诱导性关节炎的特征
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.
作者信息
Andersson E C, Hansen B E, Jacobsen H, Madsen L S, Andersen C B, Engberg J, Rothbard J B, McDevitt G S, Malmström V, Holmdahl R, Svejgaard A, Fugger L
机构信息
Departments of Clinical Immunology, Rigshospitalet, 2200 N Copenhagen, Denmark.
出版信息
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7574-9. doi: 10.1073/pnas.95.13.7574.
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.
摘要
类风湿性关节炎（RA）是一种与HLA - DR4和DR1等位基因相关的自身免疫性疾病。RA中的靶自身抗原尚不清楚，但II型胶原（CII）是一个候选抗原，该蛋白中受DR4和DR1限制的免疫显性T细胞表位对应于氨基酸261 - 273（CII 261 - 273）。我们已经确定了CII 261 - 273中MHC和T细胞受体的接触点，并提供了强有力的证据表明该肽段与先前发现的与RA相关的DR分子的肽结合特异性相对应。此外，我们证明了纯合I - Abeta0突变的HLA - DR4和人类CD4转基因小鼠对胶原诱导的关节炎高度易感，并描述了受影响关节的临床病程和组织病理学变化。
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