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The prominent role of a CDR1 somatic hypermutation for convergent IGHV3-53/3-66 antibodies in binding to SARS-CoV-2.

ABSTRACT: In the fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), monoclonal antibodies (mAbs) serve as key strategies for the rapid prevention and treatment of COVID-19. However, analysis to fully characterize functional SARS-CoV-2 mAbs is still needed. In this study, by interrogating 1,695 published or patented mAbs of human origin and validated SARS-CoV-2-binding potency, we found a highly preferential usage of IGHV3-53/3-66 germline genes that was then revealed as a distinct selectivity of SARS-CoV-2-induced humoral immunity across other coronaviruses. Moreover, among the rare somatic hypermutations, we identified a novel mutation signature of F27 to I, L, or V with high frequency, which was located in the CDR1 region of the heavy chain among IGHV3-53/3-66-encoded antibodies. This convergent mutation contributed to improving SARS-CoV-2 binding affinity and may advance our knowledge of the humoral immunity to SARS-CoV-2.

SUBMITTER: Tian X 

PROVIDER: S-EPMC9045774 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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The prominent role of a CDR1 somatic hypermutation for convergent IGHV3-53/3-66 antibodies in binding to SARS-CoV-2.

Tian Xiaolong X   Zhu Xiaoyi X   Song Wenping W   Yang Zhenlin Z   Wu Yanling Y   Ying Tianlei T  

Emerging microbes & infections 20221201 1

In the fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), monoclonal antibodies (mAbs) serve as key strategies for the rapid prevention and treatment of COVID-19. However, analysis to fully characterize functional SARS-CoV-2 mAbs is still needed. In this study, by interrogating 1,695 published or patented mAbs of human origin and validated SARS-CoV-2-binding potency, we found a highly preferential usage of IGHV3-53/3-66 germline genes that was then revealed as a distinct  ...[more]

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