Author
Listed:
- Yik Andy Yeung
(Rinat R&D, Pfizer Inc.)
- Davide Foletti
(Rinat R&D, Pfizer Inc.
Present address: 23andMe, Mountain View, California 94041, USA)
- Xiaodi Deng
(Rinat R&D, Pfizer Inc.
Present address: Bristol-Myers Squibb Inc., Redwood City, California 94063, USA)
- Yasmina Abdiche
(Rinat R&D, Pfizer Inc.)
- Pavel Strop
(Rinat R&D, Pfizer Inc.
Present address: Bristol-Myers Squibb Inc., Redwood City, California 94063, USA)
- Jacob Glanville
(Rinat R&D, Pfizer Inc.
Present address: Distributed Bio Inc., South San Francisco, California 94080, USA)
- Steven Pitts
(Rinat R&D, Pfizer Inc.
Present address: 23andMe, Mountain View, California 94041, USA)
- Kevin Lindquist
(Rinat R&D, Pfizer Inc.)
- Purnima D. Sundar
(Rinat R&D, Pfizer Inc.)
- Marina Sirota
(Rinat R&D, Pfizer Inc.
Present address: Institute for Computational Health Sciences, University of California-San Francisco, San Francisco, California 94143, USA)
- 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.
Present address: Alexo Therapeutics Inc., South San Francisco, California 94080, USA)
- David Shelton
(Rinat R&D, Pfizer Inc.)
- Arvind Rajpal
(Rinat R&D, Pfizer Inc.
Present address: Bristol-Myers Squibb Inc., Redwood City, California 94063, USA)
- Javier Chaparro-Riggers
(Rinat R&D, Pfizer Inc.)
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.
Suggested Citation
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 & , 2016.
"Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire,"
Nature Communications, Nature, vol. 7(1), pages 1-14, December.
Handle:
RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13376
DOI: 10.1038/ncomms13376
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