Proteomics

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Influence of immunoglobulin genotypes on the elicitation of SARS CoV-2 neutralizing antibodies

ABSTRACT: The human immunoglobulin heavy chain (IGH) locus is exceptionally polymorphic with high allelic diversity of variable (V) genes and structural variation affecting large regions of the locus. Thus, our germline IGHV gene and allele content is highly personal, which may influence how we respond to infections and vaccinations. Here, we coupled individualized IGHV genotyping with the isolation of monoclonal antibodies against the SARS-CoV-2 spike, focusing on the IGHV1-69 and IGHV3-30 group of genes, which were over-represented in spike-specific B cells. These genes are characterized by both allelic and copy number variations, making them ideal for expanding our understanding of inter-individual differences in antigen-specific antibody responses. We found that for the IGHV1-69*20-using CAB-I47 antibody, the allele usage was critical as germline reversion to other, highly similar, IGHV1-69 alleles abolished the neutralizing activity. Our results demonstrate that as little as single nucleotide differences between different alleles can greatly influence the biological response.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Simon Ekström  

LAB HEAD: Gunilla B. Karlsson Hedestam

PROVIDER: PXD031945 | Pride | 2023-03-11

REPOSITORIES: Pride

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The human immunoglobulin heavy-chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination. For an improved understanding of inter-individual differences in antibody responses, we isolated SARS-CoV-2 spike-specific monoclonal antibodies from convalescent health care workers, focusing on the IGHV1-69 gene, which has the highest level of allelic variation  ...[more]

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