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

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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    Cited by:

    1. Oscar L. Rodriguez & Yana Safonova & Catherine A. Silver & Kaitlyn Shields & William S. Gibson & Justin T. Kos & David Tieri & Hanzhong Ke & Katherine J. L. Jackson & Scott D. Boyd & Melissa L. Smith , 2023. "Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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