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Nat Commun. 2016 Nov 18;7:13376. doi: 10.1038/ncomms13376.

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

Author information

1
Rinat R&D, Pfizer Inc., 230 East Grand Avenue, South San Francisco, California 94080, USA.

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.

PMID:
27857134
PMCID:
PMC5120205
DOI:
10.1038/ncomms13376
[Indexed for MEDLINE]
Free PMC Article

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