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Protein Eng Des Sel. 2012 Oct;25(10):523-9. Epub 2012 Jul 15.

Germline VH/VL pairing in antibodies.

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Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.


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.

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