Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Protein Eng Des Sel. 2012 Oct;25(10):523-9. doi: 10.1093/protein/gzs043. Epub 2012 Jul 15.
Antibodies are key molecules of the adaptive immune response and are now a major class of biopharmaceuticals. Pairing of heavy and light chains is one of the ways of generating antibody diversity and, while little is known about mechanisms governing V(H)/V(L) pairing, previous studies have suggested that the germline source from which chains are paired is random. By selecting paired antibody protein sequences from human and mouse antibodies from the KabatMan database and mapping them onto their corresponding germline sequences, we find that pairing preferences do exist in the germline, but only for a small proportion of germline gene segments; others are much more promiscuous showing no preferences. The closest equivalent human and mouse gene families were identified and pairing preferences compared. This work may impact on the ability to generate more stable antibodies for use as biopharmaceuticals.
抗体是适应性免疫反应的关键分子，现在是一类主要的生物制药。重链和轻链的配对是产生抗体多样性的一种方式，尽管对于控制 V(H)/V(L) 配对的机制知之甚少，但先前的研究表明，配对的链的种系来源是随机的。通过从 KabatMan 数据库中选择来自人和小鼠的配对抗体蛋白序列，并将它们映射到相应的种系序列上，我们发现种系中确实存在配对偏好，但只存在于一小部分种系基因片段中；其他片段则更为混杂，没有偏好。确定了最接近的人源和鼠源基因家族，并对配对偏好进行了比较。这项工作可能会影响生成更稳定的生物制药用抗体的能力。
