用于识别不断演变的新冠病毒刺突蛋白的记忆B细胞库。
Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike.
作者信息
Tong Pei, Gautam Avneesh, Windsor Ian, Travers Meghan, Chen Yuezhou, Garcia Nicholas, Whiteman Noah B, McKay Lindsay G A, Lelis Felipe J N, Habibi Shaghayegh, Cai Yongfei, Rennick Linda J, Duprex W Paul, McCarthy Kevin R, Lavine Christy L, Zuo Teng, Lin Junrui, Zuiani Adam, Feldman Jared, MacDonald Elizabeth A, Hauser Blake M, Griffths Anthony, Seaman Michael S, Schmidt Aaron G, Chen Bing, Neuberg Donna, Bajic Goran, Harrison Stephen C, Wesemann Duane R
机构信息
Department of Medicine, Division of Allergy and Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
bioRxiv. 2021 Mar 10:2021.03.10.434840. doi: 10.1101/2021.03.10.434840.
Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.
记忆B细胞储备可产生针对SARS-CoV-2反复感染的保护性抗体，但从原始感染到抗原性漂移变体的影响范围尚不清楚。我们绘制了19名COVID-19康复者针对SARS-CoV-2刺突蛋白（S）的记忆B细胞受体编码单克隆抗体（mAb），发现了7个主要的mAb竞争组，针对个体间反复靶向的表位。纳入已发表和新确定的mAb-S复合物结构确定了相应的表位区域。分组与跨冠状病毒反应广度、中和效力和趋同抗体特征相关。竞争结合原始S分离株的mAb与S变体的结合存在差异，表明原本冗余的识别具有保护重要性。这些结果提供了S特异性记忆B细胞库的全球图谱，并阐明了赋予针对新出现的SARS-CoV-2变体强大抗性的特性。
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