Structural Basis of a Conventional Recognition Mode of IGHV1-69 Rheumatoid Factors.
Structural Basis of a Conventional Recognition Mode of IGHV1-69 Rheumatoid Factors.
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IGHV1-69 类风湿因子传统识别模式的结构基础。
DOI：
10.1007/5584_2020_510
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Shiroishi M.
中科院分区：
文献类型：
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作者：
Virk Karman;Yonezawa Kento;Choukate Komal;Singh Lucky;Shimizu Nobutaka;Chaudhuri Barnali;Shiroishi M.
类风湿因子(RF)是识别免疫球蛋白G(Ig G)片段结晶区(Fc)的自身抗体。在类风湿性关节炎患者中会产生遗传多样性的RF；然而，在血液疾病中，如冷球蛋白血症和B细胞淋巴瘤，来自重链V区基因和J区基因的有限组合的RF会大量产生，并与免疫球蛋白形成免疫复合物。这些遗传受限的RFs历来被用于RFs的免疫化学表征。其中，最常见的是来源于重链生殖系基因IGHV1-69的RFs。最近，从IGHV1-69衍生的RF YES8c的晶体结构在与人IgG1-Fc的络合物中被阐明。在结构和突变分析的基础上，提出了IGHV1-69来源的RFs共有的自身抗原(Ig G-Fc)的识别机制。本文综述了IGHV1-69衍生的RFs的免疫化学特征，并结合IGHV1-69衍生的中和抗体的结构特点，重点介绍了IGHV1-69衍生的RFs的识别机制。
Rheumatoid factors (RFs) are autoantibodies that recognize the fragment crystallizable (Fc) region of immunoglobulin G (IgG). Genetically diverse RFs are produced in rheumatoid arthritis patients; however, in hematologic diseases, such as cryoglobulinemia and B cell lymphoma, RFs from a limited combination of heavy chain V-region genes and J-region genes are produced in large quantities and forms immune complexes with IgG. These genetically limited RFs have historically been used for the immunochemical characterization of RFs. Among them, RFs derived from the heavy-chain germline geneIGHV1-69are the most common. Recently, the crystal structure of anIGHV1-69-derived RF named YES8c was elucidated in complex with human IgG1-Fc. Based on the structure and mutant analyses, a recognition mechanism for the autoantigen (IgG-Fc) common toIGHV1-69-derived RFs was proposed. This review summarizes the immunochemical character of theIGHV1-69-derived RFs, and then focuses on the recognition mechanism of theIGHV1-69-derived RFs, referring the structural features of theIGHV1-69-derived neutralizing antibodies.