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Mol Cell Biol. 2017 Jul 14;37(15). pii: e00202-17. doi: 10.1128/MCB.00202-17. Print 2017 Aug 1.

CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells.

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Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
Vascular Pathophysiology Research Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
CIBER Cardiovascular, Madrid, Spain.
INSERM UMRS 935, Université Paris-Sud 11, Institut André Lwoff, Villejuif, France.


Antigen presentation by dendritic cells (DCs) stimulates naive CD4+ T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II (MHC-II) molecules accumulate at MHC-II-enriched endosomal compartments and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined. Here, we show that CD9 regulates the T cell-stimulatory capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow-derived DCs (BMDCs), without affecting antigen presentation by fms-like tyrosine kinase 3 ligand (Flt3L)-dependent BMDCs. CD9 knockout (KO) GM-CSF-dependent BMDCs, which resemble monocyte-derived DCs (MoDCs), induce lower levels of T cell activation than wild-type DCs, and this effect is related to a reduction in MHC-II surface expression in CD9-deficient MoDCs. Importantly, MHC-II targeting to the plasma membrane is largely impaired in immature CD9 KO MoDCs, in which MHC-II remains arrested in acidic intracellular compartments enriched in LAMP-1 (lysosome-associated membrane protein 1), and MHC-II internalization is also blocked. Moreover, CD9 participates in MHC-II trafficking in mature MoDCs, regulating its endocytosis and recycling. Our results demonstrate that the tetraspanin CD9 specifically regulates antigenic presentation in MoDCs through the regulation of MHC-II intracellular trafficking.


CD9; MHC-II; antigen presentation; monocyte-derived dendritic cells; tetraspanin-enriched microdomain

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