Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing
Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism’s own body. Deciphering the structural mechanisms through which som...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00117/full |
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| author | Arjun K. Mishra Arjun K. Mishra Roy A. Mariuzza Roy A. Mariuzza |
| author_facet | Arjun K. Mishra Arjun K. Mishra Roy A. Mariuzza Roy A. Mariuzza |
| author_sort | Arjun K. Mishra |
| collection | DOAJ |
| description | Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism’s own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation. Crystal structures of antibodies from these lineages bound to their target antigens have revealed, at the atomic level, how antibodies evolve to penetrate the glycan shield of envelope glycoproteins, and how viruses in turn evolve to escape neutralization. Collectively, structural studies of affinity maturation have shown that increased antibody affinity can arise from any one or any combination of multiple diverse mechanisms, including improved shape complementarity at the interface with antigen, increased buried surface area upon complex formation, additional interfacial polar or hydrophobic interactions, and preorganization or rigidification of the antigen-binding site. |
| first_indexed | 2024-12-14T00:56:19Z |
| format | Article |
| id | doaj.art-ee0720a70a584c4b846949a1e7710f5c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T00:56:19Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ee0720a70a584c4b846949a1e7710f5c2022-12-21T23:23:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00117330276Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation SequencingArjun K. Mishra0Arjun K. Mishra1Roy A. Mariuzza2Roy A. Mariuzza3W. M. Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Rockville, MD, United StatesDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, United StatesW. M. Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Rockville, MD, United StatesDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, United StatesAffinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism’s own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation. Crystal structures of antibodies from these lineages bound to their target antigens have revealed, at the atomic level, how antibodies evolve to penetrate the glycan shield of envelope glycoproteins, and how viruses in turn evolve to escape neutralization. Collectively, structural studies of affinity maturation have shown that increased antibody affinity can arise from any one or any combination of multiple diverse mechanisms, including improved shape complementarity at the interface with antigen, increased buried surface area upon complex formation, additional interfacial polar or hydrophobic interactions, and preorganization or rigidification of the antigen-binding site.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00117/fullantibodyaffinity maturationsomatic hypermutationHIV-1structural biologynext-generation sequencing |
| spellingShingle | Arjun K. Mishra Arjun K. Mishra Roy A. Mariuzza Roy A. Mariuzza Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing Frontiers in Immunology antibody affinity maturation somatic hypermutation HIV-1 structural biology next-generation sequencing |
| title | Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing |
| title_full | Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing |
| title_fullStr | Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing |
| title_full_unstemmed | Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing |
| title_short | Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing |
| title_sort | insights into the structural basis of antibody affinity maturation from next generation sequencing |
| topic | antibody affinity maturation somatic hypermutation HIV-1 structural biology next-generation sequencing |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00117/full |
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