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

• Published in: Molecular and cellular biology 2017-08, Vol.37 (15)
• Main Authors: Rocha-Perugini, Vera, Martínez del Hoyo, Gloria, González-Granado, José María, Ramírez-Huesca, Marta, Zorita, Virginia, Rubinstein, Eric, Boucheix, Claude, Sánchez-Madrid, Francisco
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; CD4-Positive T-Lymphocytes - immunology; CD9; Cell Movement; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Gene Deletion; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Immunology; Life Sciences; Lymphocyte Activation; Membrane Proteins - immunology; MHC-II; Mice, Inbred C57BL; monocyte-derived dendritic cells; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Protein Transport; Spotlight; Tetraspanin 29 - genetics; Tetraspanin 29 - immunology; tetraspanin-enriched microdomain
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1128/MCB.00202-17

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.