Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.
Nat Commun
; 7: 13376, 2016 11 18.
Article
in En
| MEDLINE
| ID: mdl-27857134
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.
Full text:
1
Database:
MEDLINE
Main subject:
Staphylococcal Infections
/
Bacterial Proteins
/
Virulence Factors
/
Antibodies, Bacterial
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Year:
2016
Type:
Article