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Frequent use of IGH...
Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses
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Pushparaj, P (författare)
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- Nicoletto, A (författare)
- Karolinska Institutet
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- Dopico, XC (författare)
- Karolinska Institutet
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- Sheward, DJ (författare)
- Karolinska Institutet
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Kim, S (författare)
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Ekström, S (författare)
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- Murrell, B (författare)
- Karolinska Institutet
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- Corcoran, M (författare)
- Karolinska Institutet
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- Karlsson Hedestam, GB (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2023-03-01
- 2023
- Engelska.
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Ingår i: Frontiers in virology (Lausanne, Switzerland). - : Frontiers Media SA. - 2673-818X. ; 3, s. 1128253-
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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- 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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