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J Am Chem Soc. 2013 Jul 10;135(27):9980-3. doi: 10.1021/ja402927u. Epub 2013 Jun 26.

Mutational analysis of 48G7 reveals that somatic hypermutation affects both antibody stability and binding affinity.

Author information

1
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Abstract

The monoclonal antibody 48G7 differs from its germline precursor by 10 somatic mutations, a number of which appear to be functionally silent. We analyzed the effects of individual somatic mutations and combinations thereof on both antibody binding affinity and thermal stability. Individual somatic mutations that enhance binding affinity to hapten decrease the stability of the germline antibody; combining these binding mutations produced a mutant with high affinity for hapten but exceptionally low stability. Adding back each of the remaining somatic mutations restored thermal stability. These results, in conjunction with recently published studies, suggest an expanded role for somatic hypermutation in which both binding affinity and stability are optimized during clonal selection.

PMID:
23795814
PMCID:
PMC3773045
DOI:
10.1021/ja402927u
[Indexed for MEDLINE]
Free PMC Article

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