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

被引：8
|
作者：
Tian, Xiaolong [1 ]
Zhu, Xiaoyi [1 ]
Song, Wenping [1 ]
Yang, Zhenlin [2 ,3 ,4 ]
Wu, Yanling [1 ,2 ]
Ying, Tianlei [1 ,2 ,4 ]
机构：
[1] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, MOE NHC Key Lab Med Mol Virol, Shanghai 200032, Peoples R China
[2] Shanghai Engn Res Ctr Synthet Immunol, Shanghai 200032, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Dept Pulm Med, Shanghai, Peoples R China
[4] Shanghai Key Lab Lung Inflammat & Injury, Shanghai 200032, Peoples R China
来源：
EMERGING MICROBES & INFECTIONS | 2022年 / 11卷 / 01期
基金：
国家重点研发计划;
关键词：
SARS-CoV-2; monoclonal antibody; somatic hypermutation; IGHV3-53; antibody affinity;
D O I：
10.1080/22221751.2022.2063074
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：1186 / 1190
页数：5
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