Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire

Yik Andy Yeung (), Davide Foletti, Xiaodi Deng, Yasmina Abdiche, Pavel Strop, Jacob Glanville, Steven Pitts, Kevin Lindquist, Purnima D. Sundar, Marina Sirota, Adela Hasa-Moreno, Amber Pham, Jody Melton Witt, Irene Ni, Jaume Pons, David Shelton, Arvind Rajpal and Javier Chaparro-Riggers ()
Additional contact information
Yik Andy Yeung: Rinat R&D, Pfizer Inc.
Davide Foletti: Rinat R&D, Pfizer Inc.
Xiaodi Deng: Rinat R&D, Pfizer Inc.
Yasmina Abdiche: Rinat R&D, Pfizer Inc.
Pavel Strop: Rinat R&D, Pfizer Inc.
Jacob Glanville: Rinat R&D, Pfizer Inc.
Steven Pitts: Rinat R&D, Pfizer Inc.
Kevin Lindquist: Rinat R&D, Pfizer Inc.
Purnima D. Sundar: Rinat R&D, Pfizer Inc.
Marina Sirota: Rinat R&D, Pfizer Inc.
Adela Hasa-Moreno: Rinat R&D, Pfizer Inc.
Amber Pham: Rinat R&D, Pfizer Inc.
Jody Melton Witt: Rinat R&D, Pfizer Inc.
Irene Ni: Rinat R&D, Pfizer Inc.
Jaume Pons: Rinat R&D, Pfizer Inc.
David Shelton: Rinat R&D, Pfizer Inc.
Arvind Rajpal: Rinat R&D, Pfizer Inc.
Javier Chaparro-Riggers: Rinat R&D, Pfizer Inc.

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13376

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DOI: 10.1038/ncomms13376

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