1. Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.
- Author
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Yeung, Yik Andy, Foletti, Davide, Deng, Xiaodi, Abdiche, Yasmina, Strop, Pavel, Glanville, Jacob, Pitts, Steven, Lindquist, Kevin, Sundar, Purnima D, Sirota, Marina, Hasa-Moreno, Adela, Pham, Amber, Melton Witt, Jody, Ni, Irene, Pons, Jaume, Shelton, David, Rajpal, Arvind, and Chaparro-Riggers, Javier
- Subjects
B-Lymphocytes ,Humans ,Staphylococcus aureus ,Staphylococcal Infections ,Bacterial Proteins ,Virulence Factors ,Antibodies ,Bacterial ,Immunologic Memory ,Protein Conformation ,Models ,Molecular ,Antibodies ,Neutralizing ,RNA ,Long Noncoding ,Protein Domains ,Antibodies ,Bacterial ,Neutralizing ,Models ,Molecular ,RNA ,Long Noncoding - 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.
- Published
- 2016