Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

Handle URI:
http://hdl.handle.net/10754/626694
Title:
Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding
Authors:
Di Palma, Francesco ( 0000-0002-3758-9045 ) ; Tramontano, Anna
Abstract:
The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.
Citation:
Di Palma F, Tramontano A (2017) Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding. FEBS Letters 591: 2936–2950. Available: http://dx.doi.org/10.1002/1873-3468.12774.
Publisher:
Wiley-Blackwell
Journal:
FEBS Letters
KAUST Grant Number:
k1038
Issue Date:
3-Aug-2017
DOI:
10.1002/1873-3468.12774
Type:
Article
ISSN:
0014-5793
Sponsors:
The simulations were performed using the computational resources provided by the KAUST Supercomputer Laboratory (project k1038). We thank the support of NVIDIA Corporation for the award of the NVIDIA Hardware Grant (Tesla K40 GPU) used for this research. This article is dedicated to Professor Anna Tramontano, for her very enlightening and inspiring view on research, in memoriam.
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Full metadata record

DC FieldValue Language
dc.contributor.authorDi Palma, Francescoen
dc.contributor.authorTramontano, Annaen
dc.date.accessioned2018-01-04T07:51:39Z-
dc.date.available2018-01-04T07:51:39Z-
dc.date.issued2017-08-03en
dc.identifier.citationDi Palma F, Tramontano A (2017) Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding. FEBS Letters 591: 2936–2950. Available: http://dx.doi.org/10.1002/1873-3468.12774.en
dc.identifier.issn0014-5793en
dc.identifier.doi10.1002/1873-3468.12774en
dc.identifier.urihttp://hdl.handle.net/10754/626694-
dc.description.abstractThe investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.en
dc.description.sponsorshipThe simulations were performed using the computational resources provided by the KAUST Supercomputer Laboratory (project k1038). We thank the support of NVIDIA Corporation for the award of the NVIDIA Hardware Grant (Tesla K40 GPU) used for this research. This article is dedicated to Professor Anna Tramontano, for her very enlightening and inspiring view on research, in memoriam.en
dc.publisherWiley-Blackwellen
dc.subject8F9en
dc.subjectAD-2S1en
dc.subjectantibody affinity maturationen
dc.subjectHCMVen
dc.subjectsomatic hypermutationen
dc.titleDynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen bindingen
dc.typeArticleen
dc.identifier.journalFEBS Lettersen
dc.contributor.institutionDepartment of Physics; Sapienza - Università di Roma; Italyen
dc.contributor.institutionIstituto Pasteur Italia - Fondazione Cenci Bolognetti; Roma Italyen
kaust.grant.numberk1038en
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