Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Yuan M 

PROVIDER: S-EPMC10636607 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Yuan Meng M   Feng Ziqi Z   Lv Huibin H   So Natalie N   Shen Ivana R IR   Tan Timothy J C TJC   Teo Qi Wen QW   Ouyang Wenhao O WO   Talmage Logan L   Wilson Ian A IA   Wu Nicholas C NC  

Cell reports 20230930 10


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 experim  ...[more]

Similar Datasets

| S-EPMC10274783 | biostudies-literature
| S-EPMC3057935 | biostudies-literature
| S-EPMC11384754 | biostudies-literature
| S-EPMC3949579 | biostudies-literature
| S-EPMC5420356 | biostudies-literature
| S-EPMC11865429 | biostudies-literature
| S-EPMC5486809 | biostudies-literature
| S-EPMC8798060 | biostudies-literature
| S-EPMC6851129 | biostudies-literature
| S-EPMC1592471 | biostudies-literature