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

Francesco Di Palma; Anna Tramontano

doi:10.1002/1873-3468.12774

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

Francesco Di Palma, Anna Tramontano

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2936-2950
Number of pages	15
Journal	FEBS Letters
Volume	591
Issue number	18
DOIs	https://doi.org/10.1002/1873-3468.12774
State	Published - Aug 30 2017
Externally published	Yes

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title = "Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding",

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.",

author = "{Di Palma}, Francesco and Anna Tramontano",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): k1038 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

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doi = "10.1002/1873-3468.12774",

language = "English (US)",

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AU - Di Palma, Francesco

AU - Tramontano, Anna

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): k1038 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2017/8/30

Y1 - 2017/8/30

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/626694

UR - http://doi.wiley.com/10.1002/1873-3468.12774

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VL - 591

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JO - FEBS Letters

JF - FEBS Letters

IS - 18

ER -

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

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