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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural mechanism for affinity maturation of an anti-lysozyme antibody
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Structural mechanism for affinity maturation of an anti-lysozyme antibody

机译：抗溶菌酶抗体亲和力成熟的结构机制

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In the immune response against a typical T cell-dependent protein antigen, the affinity maturation process is fast and is associated with the early class switch from IgM to IgG. As such, a comprehension of the molecular basis of affinity maturation could be of great importance in biomedical and biotechnological applications. Affinity maturation of anti-protein antibodies has been reported to be the result of small structural changes, mostly confined to the periphery of the antigen-combining site. However, little is understood about how these small structural changes account for the increase in the affinity toward the antigen. Herein, we present the three-dimensional structure of the Fab fragment from BALB/c mouse mAb F10.6.6 in complex with the antigen lysozyme. This antibody was obtained from a long-term exposure to the antigen. mAb F10.6.6, and the previously described antibody D44.11, are the result of identical or nearly identical somatic recombination events. However, different mutations in the framework and variable regions result in an approximate to10(3) higher affinity for the F10.6.6 antibody. The comparison of the three-dimensional structures of these Fablysozyme complexes reveals that the affinity maturation produces a fine tuning of the complementarity of the antigen-combining site toward the epitope, explaining at the molecular level how the immune system is able to increase the affinity of an anti-protein antibody to subnanomolar levels. [References: 43]
机译：在针对典型的T细胞依赖性蛋白抗原的免疫应答中，亲和力成熟过程快速，并且与从IgM到IgG的早期类别转换相关。因此，对亲和力成熟的分子基础的理解在生物医学和生物技术应用中可能非常重要。据报道，抗蛋白抗体的亲和力成熟是结构变化很小的结果，主要是局限于抗原结合位点的外围。然而，对于这些小的结构变化如何解释对抗原的亲和力增加的了解很少。在这里，我们提出了来自BALB / c小鼠mAb F10.6.6与抗原溶菌酶复合的Fab片段的三维结构。该抗体是从长期暴露于抗原中获得的。 mAb F10.6.6和先前描述的抗体D44.11是相同或几乎相同的体细胞重组事件的结果。但是，框架和可变区中的不同突变导致对F10.6.6抗体的亲和力提高了约10（3）。这些Fablesozyme复杂的三维结构的比较表明，亲和力成熟产生抗原结合位点向表位的互补性的微调，在分子水平上解释了免疫系统如何能够增加抗原的结合。一种抗蛋白质的抗纳摩尔水平的抗体。 [参考：43]

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