Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity
Summary: 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 anal...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723012068 |
| _version_ | 1797669930788716544 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Meng Yuan |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-11T20:52:09Z |
| format | Article |
| id | doaj.art-d1d4dec35ad34509ab52271c250886a8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T20:52:09Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d1d4dec35ad34509ab52271c250886a82023-10-01T05:58:18ZengElsevierCell Reports2211-12472023-10-014210113194Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivityMeng Yuan0Ziqi Feng1Huibin Lv2Natalie So3Ivana R. Shen4Timothy J.C. Tan5Qi Wen Teo6Wenhao O. Ouyang7Logan Talmage8Ian A. Wilson9Nicholas C. Wu10Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USACenter for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723012068CP: Immunology |
| spellingShingle | 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 Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity Cell Reports CP: Immunology |
| title | Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity |
| title_full | Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity |
| title_fullStr | Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity |
| title_full_unstemmed | Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity |
| title_short | Widespread impact of immunoglobulin V-gene allelic polymorphisms on antibody reactivity |
| title_sort | widespread impact of immunoglobulin v gene allelic polymorphisms on antibody reactivity |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723012068 |
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