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

Autor:	Pushparaj P; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Nicoletto A; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Dopico XC; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Sheward DJ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Kim S; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Ekström S; Department of Biomedical Engineering, Lund University, Lund, Sweden., Murrell B; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Corcoran M; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Karlsson Hedestam GB; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in virology [Front Virol] 2023 Mar 01; Vol. 3, pp. 1128253.
DOI:	10.3389/fviro.2023.1128253
Abstrakt:	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 spikespecific 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. Competing Interests: Conflict of interest MC and GKH are founders of ImmuneDiscover Sweden. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Databáze:	MEDLINE
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