Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain

Timothy J.C. Tan; Meng Yuan; Kaylee Kuzelka; Gilberto C. Padron; Jacob R. Beal; Xin Chen; Yiquan Wang; Joel Rivera-Cardona; Xueyong Zhu; Beth M. Stadtmueller; Christopher B. Brooke; Ian A. Wilson; Nicholas C. Wu

doi:10.1101/2021.01.26.428356

Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain

Timothy J.C. Tan, Meng Yuan, Kaylee Kuzelka, Gilberto C. Padron, Jacob R. Beal, Xin Chen, Yiquan Wang, Joel Rivera-Cardona, Xueyong Zhu, Beth M. Stadtmueller, Christopher B. Brooke, Ian A. Wilson, Nicholas C. Wu

Research output: Contribution to journal › Article › peer-review

Abstract

Since the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short complementarity-determining region (CDR) H3. Germline-encoded sequence motifs in heavy chain CDRs H1 and H2 have a major function, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, is not clear. Here, we identify two public clonotypes of IGHV3-53/3-66 RBD antibodies with a 9-residue CDR H3 that pair with different light chains. Distinct sequence motifs on CDR H3 are present in the two public clonotypes that seem to be related to differential light chain pairing. Additionally, we show that Y58F is a common somatic hypermutation that results in increased binding affinity of IGHV3-53/3-66 RBD antibodies with a short CDR H3. These results advance understanding of the antibody response to SARS-CoV-2.

Original language	English (US)
Article number	3815
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1101/2021.01.26.428356 https://doi.org/10.1038/s41467-021-24123-7
State	Published - Dec 2021

Keywords

Novel coronavirus
COVID-19
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus
2019-nCoV
Pandemic

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Online availability

10.1101/2021.01.26.428356License: CC BY
10.1038/s41467-021-24123-7License: CC BY

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Tan, T. J. C., Yuan, M., Kuzelka, K., Padron, G. C., Beal, J. R., Chen, X., Wang, Y., Rivera-Cardona, J., Zhu, X., Stadtmueller, B. M., Brooke, C. B., Wilson, I. A., & Wu, N. C. (2021). Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain. Nature Communications, 12(1), Article 3815. https://doi.org/10.1101/2021.01.26.428356, https://doi.org/10.1038/s41467-021-24123-7

Tan, TJC, Yuan, M, Kuzelka, K, Padron, GC, Beal, JR, Chen, X, Wang, Y, Rivera-Cardona, J, Zhu, X, Stadtmueller, BM , Brooke, CB, Wilson, IA & Wu, NC 2021, 'Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain', Nature Communications, vol. 12, no. 1, 3815. https://doi.org/10.1101/2021.01.26.428356, https://doi.org/10.1038/s41467-021-24123-7

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title = "Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain",

abstract = "Since the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short complementarity-determining region (CDR) H3. Germline-encoded sequence motifs in heavy chain CDRs H1 and H2 have a major function, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, is not clear. Here, we identify two public clonotypes of IGHV3-53/3-66 RBD antibodies with a 9-residue CDR H3 that pair with different light chains. Distinct sequence motifs on CDR H3 are present in the two public clonotypes that seem to be related to differential light chain pairing. Additionally, we show that Y58F is a common somatic hypermutation that results in increased binding affinity of IGHV3-53/3-66 RBD antibodies with a short CDR H3. These results advance understanding of the antibody response to SARS-CoV-2.",

keywords = "Novel coronavirus, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus, 2019-nCoV, Pandemic",

author = "Tan, {Timothy J.C.} and Meng Yuan and Kaylee Kuzelka and Padron, {Gilberto C.} and Beal, {Jacob R.} and Xin Chen and Yiquan Wang and Joel Rivera-Cardona and Xueyong Zhu and Stadtmueller, {Beth M.} and Brooke, {Christopher B.} and Wilson, {Ian A.} and Wu, {Nicholas C.}",

note = "Funding Information: We thank the Roy J. Carver Biotechnology Center at the University of Illinois at Urbana-Champaign for assistance with fluorescence-activated cell sorting and next-generation sequencing. This work was supported by NIH R00 AI139445 (N.C.W.), and Bill and Melinda Gates Foundation INV-004923 (I.A.W.). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Beal, Jacob R.

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AU - Wang, Yiquan

AU - Rivera-Cardona, Joel

AU - Zhu, Xueyong

AU - Stadtmueller, Beth M.

AU - Brooke, Christopher B.

AU - Wilson, Ian A.

AU - Wu, Nicholas C.

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N2 - Since the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short complementarity-determining region (CDR) H3. Germline-encoded sequence motifs in heavy chain CDRs H1 and H2 have a major function, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, is not clear. Here, we identify two public clonotypes of IGHV3-53/3-66 RBD antibodies with a 9-residue CDR H3 that pair with different light chains. Distinct sequence motifs on CDR H3 are present in the two public clonotypes that seem to be related to differential light chain pairing. Additionally, we show that Y58F is a common somatic hypermutation that results in increased binding affinity of IGHV3-53/3-66 RBD antibodies with a short CDR H3. These results advance understanding of the antibody response to SARS-CoV-2.

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Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain

Abstract

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Antibodies from original strain COVID-19 infection don't bind to variants, study finds

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Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain

Abstract

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ASJC Scopus subject areas

Online availability

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Antibodies from original strain COVID-19 infection don't bind to variants, study finds

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