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

Nat Commun. 2021 Jun 21;12(1):3815. doi: 10.1038/s41467-021-24123-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / immunology*
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / metabolism
  • Antibody Formation
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • COVID-19 / virology
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / immunology
  • Complementarity Determining Regions / metabolism
  • Crystallography, X-Ray
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Domains
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Antibodies, Neutralizing
  • Complementarity Determining Regions
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2