Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain.
Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain.
复制标题
人类自身抗体与 T 细胞受体 β 链的合成自身抗原发生反应。
DOI：
10.1073/pnas.89.8.3325
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发表时间：
1992
影响因子：
11.1
通讯作者：
Edmundson,AB
中科院分区：
文献类型：
--
作者：
Marchalonis,JJ;Kaymaz,H;Dedeoglu,F;Schluter,SF;Yocum,DE;Edmundson,AB
我们使用合成重叠肽作图，结合分子模型分析人类自然产生的针对人类t细胞受体β链的IgG抗体，并在分子的三维结构中定位识别的肽自身抗原。健康个体产生低水平的抗t细胞受体肽的抗体，而这些抗体在自身免疫性疾病中可能会增加。我们详细描述了反应性，因为IgG分子与自身肽反应发生在静脉注射免疫球蛋白的制备中，并且可以通过免疫亲和层析分离。天然IgG抗体针对三种主要肽。一个对应于变量区域的第一个互补决定区域。第二框架对应于可变区域的第三框架。第三个位于恒定区域，预计是一个从β桶结构延伸出来的回路。这种肽将在-链恒定区和免疫球蛋白轻链的恒定区之间给出特征结构区别，而-链是同源的。正常多克隆IgG的一小部分含有kappa链和lambda链，具有结合这些肽的能力。这种活性与抗体类似，因为它局限于Fab片段，并且能够区分与不同的β链可变区基因相对应的同源合成肽。我们提出，识别和调节过程自然发生平行的免疫网络的生产抗体的调节。
We used mapping with synthetic overlapping peptides in combination with molecular modeling to analyze the IgG antibodies that humans naturally produce against human T-cell receptor beta chains and to localize the recognized peptide autoantigens in the three-dimensional structure of the molecule. Healthy individuals produce low levels of antibodies against T-cell receptor peptides, and these can be increased in autoimmune diseases. We characterized the reactivities in detail because IgG molecules reactive with self peptides occur in preparations of intravenous immunoglobulin and can be isolated by immunoaffinity chromatography. Natural IgG antibodies were directed against three major peptides. One corresponds to the first complementarity-determining region of the variable region. A second corresponds to the third framework of the variable region. The third is located in the constant region and is predicted to be a loop that extends out of the beta-barrel structure. This peptide is one that would give a characteristic structural distinction between the beta-chain constant region and the constant regions of immunoglobulin light chains to which beta chains are homologous. The capacity to bind these peptides is found in small fractions of normal polyclonal IgG, which contains both kappa chains and lambda chains. The activity is antibody-like in being confined to the Fab fragment and in its capacity to discriminate among homologous synthetic peptides corresponding to distinct beta-chain variable-region genes. We propose that a recognition and regulatory process naturally occurs that parallels the immune network for the regulation of the production of antibodies.