Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity.
Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity.
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DOI：
10.1016/j.celrep.2023.113194
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发表时间：
2023-10-31
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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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. Analysis of V-gene allelic polymorphisms in 1,048 antibody-antigen complex structures Many antibodies contain allelic polymorphisms predicted to disrupt binding These include antibodies with different V genes and to different pathogens Some broadly neutralizing antibodies depend on minor V-gene allelic polymorphisms By analyzing >1,000 publicly available antibody-antigen complex structures, Yuan et al. demonstrate that antibody binding activity is often influenced by V-gene allelic polymorphisms. This result provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.
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DOI：
10.1126/science.aar5304
发表时间：
2018-06-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Imkeller K;Scally SW;Bosch A;Martí GP;Costa G;Triller G;Murugan R;Renna V;Jumaa H;Kremsner PG;Sim BKL;Hoffman SL;Mordmüller B;Levashina EA;Julien JP;Wardemann H
通讯作者：
Wardemann H
影响因子：
14.9
作者：
Benson DA;Cavanaugh M;Clark K;Karsch-Mizrachi I;Ostell J;Pruitt KD;Sayers EW
通讯作者：
Sayers EW
影响因子：
6
作者：
Buß O;Rudat J;Ochsenreither K
通讯作者：
Ochsenreither K
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
6.4
作者：
Bennett, Monique R.;Dong, Jinhui;Crowe, James E., Jr.
通讯作者：
Crowe, James E., Jr.