Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain
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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.
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SciScore for 10.1101/2021.01.26.428356: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Literature mining for antibodies to SARS-CoV-2 RBD: Sequences of anti-SARS-CoV-2 RBD from convalescent patients infected with SARS-CoV-2 were obtained from published articles20–40 anti-SARS-CoV-2suggested: NoneSubsequently, 1 μg of PE anti-human IgG Fc antibody (clone HP6017, BioLegend, Cat. No. 409304) buffer-exchanged into 1x PBS was added to yeast. PE anti-human IgG Fc antibodysuggested: (BioLegend Cat# 409304, RRID:AB_10895907)anti-human IgGsuggested: (BioLegend Cat# 409304, RRID:AB_1089590…SciScore for 10.1101/2021.01.26.428356: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Literature mining for antibodies to SARS-CoV-2 RBD: Sequences of anti-SARS-CoV-2 RBD from convalescent patients infected with SARS-CoV-2 were obtained from published articles20–40 anti-SARS-CoV-2suggested: NoneSubsequently, 1 μg of PE anti-human IgG Fc antibody (clone HP6017, BioLegend, Cat. No. 409304) buffer-exchanged into 1x PBS was added to yeast. PE anti-human IgG Fc antibodysuggested: (BioLegend Cat# 409304, RRID:AB_10895907)anti-human IgGsuggested: (BioLegend Cat# 409304, RRID:AB_10895907)Software and Algorithms Sentences Resources IgBlast was used to identify somatic hypermutations and analyze IGHJ gene usage72. IgBlastsuggested: (IgBLAST, RRID:SCR_002873)PEAR was used for merging the forward and reverse reads82. PEARsuggested: (PEAR, RRID:SCR_003776)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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