Widespread impact of immunoglobulin V gene allelic polymorphisms on antibody reactivity.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
07 Jun 2023
07 Jun 2023
Historique:
medline:
19
6
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
epublish
Résumé
The ability of human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V gene (IGV) allelic polymorphisms. However, previous studies have provided only a limited number of examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many IGV allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiment further demonstrates that paratope allelic mutations on both heavy and light chain often abolish antibody binding. We also illustrate the importance of minor IGV allelic variants with low frequency in several broadly neutralizing antibodies to SARS-CoV-2 and influenza virus. Overall, this study not only highlights the pervasive impact of IGV allelic polymorphisms on antibody binding, but also provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.
Identifiants
pubmed: 37333077
doi: 10.1101/2023.06.06.543969
pmc: PMC10274783
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93021C00015
Pays : United States
Organisme : Bill & Melinda Gates Foundation
ID : INV-004923
Pays : United States
Organisme : NCCIH NIH HHS
ID : DP2 AT011966
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI167910
Pays : United States
Commentaires et corrections
Type : UpdateIn
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