Endocytosed soluble cowpox virus protein CPXV012 inhibits antigen cross-presentation in human monocyte-derived dendritic cells.
Immunol Cell Biol
; 96(2): 137-148, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29363167
ABSTRACT
Viruses may interfere with the MHC class I antigen presentation pathway in order to avoid CD8+ T cell-mediated immunity. A key target within this pathway is the peptide transporter TAP. This transporter plays a central role in MHC class I-mediated peptide presentation of endogenous antigens. In addition, TAP plays a role in antigen cross-presentation of exogenously derived antigens by dendritic cells (DCs). In this study, a soluble form of the cowpox virus TAP inhibitor CPXV012 is synthesized for exogenous delivery into the antigen cross-presentation route of human monocyte-derived (mo)DCs. We show that soluble CPXV012 localizes to TAP+ compartments that carry internalized antigen and is a potent inhibitor of antigen cross-presentation. CPXV012 stimulates the prolonged deposition of antigen fragments in storage compartments of moDCs, as a result of reduced endosomal acidification and reduced antigen proteolysis when soluble CPXV012 is present. Thus, a dual function can be proposed for CPXV012 inhibition of TAP-mediated peptide transport and inhibition of endosomal antigen degradation. We propose this second function for soluble CPXV012 can serve to interfere with antigen cross-presentation in a peptide transport-independent manner.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
Células Dendríticas
/
Monócitos
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Vírus da Varíola Bovina
/
Apresentação de Antígeno
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Apresentação Cruzada
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Endocitose
Limite:
Humans
Idioma:
En
Revista:
Immunol Cell Biol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Holanda