MHC class II presentation is controlled by the lysosomal small GTPase, Arl8b.
J Immunol
; 194(5): 2079-88, 2015 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-25637027
ABSTRACT
Dendritic cells (DCs) are specialized APCs with the ability to prime naive T cells. DCs first sample Ags from the environment and then orchestrate their processing and loading onto MHC class II (MHC II) Ag-presenting molecules in lysosomes. Once MHC II molecules have bound a peptide, the MHC II-peptide complex is delivered to the cell surface for presentation to CD4(+) T cells. Regulation of Ag uptake via macropinocytosis and phagocytosis has been extensively studied, as well as trafficking in early endocytic vesicles notably regulated by the small GTPase Rab5 and its effectors. However, little is known about the regulators of Ag delivery from early endosomes to lysosomal compartments where the proper pH, proteases, MHC II, invariant chain, and HLA-DM reside, awaiting exogenous Ags for loading. In this article, we report the crucial role of the small GTPase ADP-ribosylation factor-like 8b (Arl8b) in MHC II presentation in DCs. We show for the first time, to our knowledge, that Arl8b localizes to MHC II compartments in DCs and regulates formation of MHC II-peptide complexes. Arl8b-silenced DCs display a defect in MHC II-Ag complex formation and its delivery to the cell surface during infection resulting in a defect in T cell recognition. Our results highlight the role of Arl8b as a trafficking regulator of the late stage of complex formation and MHC II presentation in DCs.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Linfócitos T CD4-Positivos
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Antígenos de Histocompatibilidade Classe II
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Apresentação de Antígeno
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Fatores de Ribosilação do ADP
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Lisossomos
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2015
Tipo de documento:
Article