Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity

Meng Yuan, Ziqi Feng, Huibin Lv, Natalie So, Ivana R. Shen, Timothy J.C. Tan, Qi Wen Teo, Wenhao O. Ouyang, Logan Talmage, Ian A. Wilson, Nicholas C. Wu

Research output: Contribution to journalArticlepeer-review


The ability of the human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V-gene allelic polymorphisms. However, previous studies have provided only limited examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many V-gene allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiments further demonstrate that paratope allelic polymorphisms on both heavy and light chains often abolish antibody binding. We also illustrate the importance of minor V-gene allelic polymorphisms with low frequency in several broadly neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Overall, this study not only highlights the pervasive impact of V-gene 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.

Original languageEnglish (US)
Article number113194
JournalCell Reports
Issue number10
StatePublished - Oct 31 2023


  • B cells
  • CP: Immunology
  • allelic polymorphism
  • antibody
  • immunoglobulin V gene
  • paratope
  • structural biology
  • virus

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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