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Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses

Pushparaj, Pradeepa ; Nicoletto, Andrea ; Castro Dopico, Xaquin ; Sheward, Daniel J. ; Kim, Sungyong ; Ekström, Simon LU ; Murrell, Ben ; Corcoran, Martin and Karlsson Hedestam, Gunilla B. (2023) In Frontiers in Virology 3.
Abstract

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly... (More)

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allelic diversity, antibodies, copy number variation, immunoglobulin germline genes, SARS-CoV-2
in
Frontiers in Virology
volume
3
article number
1128253
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85195260577
  • pmid:37041983
ISSN
2673-818X
DOI
10.3389/fviro.2023.1128253
language
English
LU publication?
yes
id
cb811507-01fe-461a-8e20-ce40588dcfc5
date added to LUP
2024-10-09 15:54:44
date last changed
2025-07-17 16:16:22
@article{cb811507-01fe-461a-8e20-ce40588dcfc5,
  abstract     = {{<p>The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody.</p>}},
  author       = {{Pushparaj, Pradeepa and Nicoletto, Andrea and Castro Dopico, Xaquin and Sheward, Daniel J. and Kim, Sungyong and Ekström, Simon and Murrell, Ben and Corcoran, Martin and Karlsson Hedestam, Gunilla B.}},
  issn         = {{2673-818X}},
  keywords     = {{allelic diversity; antibodies; copy number variation; immunoglobulin germline genes; SARS-CoV-2}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Virology}},
  title        = {{Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses}},
  url          = {{http://dx.doi.org/10.3389/fviro.2023.1128253}},
  doi          = {{10.3389/fviro.2023.1128253}},
  volume       = {{3}},
  year         = {{2023}},
}