Journal article
Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses
- 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 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.5MB, Terms of use)
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- Publisher copy:
- 10.3389/fviro.2023.1128253
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Virology More from this journal
- Volume:
- 3
- Article number:
- 1128253
- Publication date:
- 2023-03-01
- Acceptance date:
- 2023-01-31
- DOI:
- EISSN:
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2673-818X
- Language:
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English
- Keywords:
- Pubs id:
-
1804071
- Local pid:
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pubs:1804071
- Deposit date:
-
2024-03-14
Terms of use
- Copyright holder:
- Pushparaj et al
- Copyright date:
- 2023
- Rights statement:
- © 2023 Pushparaj, Nicoletto, Castro Dopico, Sheward, Kim, Ekström, Murrell, Corcoran and Karlsson Hedestam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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