Identifying functional anti-Staphylococcus aureus antibodies by sequencing antibody repertoires of patient plasmablasts.
Clin Immunol
; 152(1-2): 77-89, 2014.
Article
em En
| MEDLINE
| ID: mdl-24589749
ABSTRACT
Infection by Staphylococcus aureus is on the rise, and there is a need for a better understanding of host immune responses that combat S. aureus. Here we use DNA barcoding to enable deep sequencing of the paired heavy- and light-chain immunoglobulin genes expressed by individual plasmablasts derived from S. aureus-infected humans. Bioinformatic analysis of the antibody repertoires revealed clonal families of heavy-chain sequences and enabled rational selection of antibodies for recombinant expression. Of the ten recombinant antibodies produced, seven bound to S. aureus, of which four promoted opsonophagocytosis of S. aureus. Five of the antibodies bound to known S. aureus cell-surface antigens, including fibronectin-binding protein A. Fibronectin-binding protein A-specific antibodies were isolated from two independent S. aureus-infected patients and mediated neutrophil killing of S. aureus in in vitro assays. Thus, our DNA barcoding approach enabled efficient identification of antibodies involved in protective host antibody responses against S. aureus.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
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Staphylococcus aureus
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Cadeias Pesadas de Imunoglobulinas
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Cadeias Leves de Imunoglobulina
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Anticorpos Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article