Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.
Immunity
; 56(1): 193-206.e7, 2023 01 10.
Article
in English
| MEDLINE | ID: covidwho-2149893
ABSTRACT
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 of all IGHV genes. The IGHV1-69∗20-using CAB-I47 antibody and two similar antibodies isolated from an independent donor were critically dependent on allele usage. Neutralization was retained when reverting the V region to the germline IGHV1-69∗20 allele but lost when reverting to other IGHV1-69 alleles. Structural data confirmed that two germline-encoded polymorphisms, R50 and F55, in the IGHV1-69 gene were required for high-affinity receptor-binding domain interaction. These results demonstrate that polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Immunity
Journal subject:
Allergy and Immunology
Year:
2023
Document Type:
Article
Affiliation country:
J.immuni.2022.12.005
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