Dramatic activation of an antibody by a single amino acid change in framework
Dramatic activation of an antibody by a single amino acid change in framework
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London: Nature Publishing Group UK
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English
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London: Nature Publishing Group UK
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Antibody function is typically entirely dictated by the Complementarity Determining Regions (CDRs) that directly bind to the antigen, while the framework region acts as a scaffold for the CDRs and maintains overall structure of the variable domain. We recently reported that the rabbit monoclonal antibody 4A11 (rbt4A11) disrupts signaling through both TGFβ2 and TGFβ3 (Sun et al. in Sci Transl Med, 2021.
https://doi.org/10.1126/scitranslmed.abe0407
). Here, we report a dramatic, unexpected discovery during the humanization of rbt4A11 where, two variants of humanized 4A11 (h4A11), v2 and v7 had identical CDRs, maintained high affinity binding to TGFβ2/3, yet exhibited distinct differences in activity. While h4A11.v7 completely inhibited TGFβ2/3 signaling like rbt4A11, h4A11.v2 did not....
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Dramatic activation of an antibody by a single amino acid change in framework
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TN_cdi_doaj_primary_oai_doaj_org_article_0b851df1980f44c9ad9fd78eb3510ab2
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https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_doaj_primary_oai_doaj_org_article_0b851df1980f44c9ad9fd78eb3510ab2
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2045-2322
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2045-2322
DOI
10.1038/s41598-021-01530-w
