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

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.

SUBMITTER: Sun SB

PROVIDER: S-EPMC3773045 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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

Sun Sophie B SB Sen Shiladitya S Kim Nam-Jung NJ Magliery Thomas J TJ Schultz Peter G PG Wang Feng F

Journal of the American Chemical Society 20130626 27

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 lo ...[more]

PMID: 23795814

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Dataset Information

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

Publications

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

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