MARCH9‐mediated ubiquitination regulates MHC I export from the TGN

Francesca de Angelis Rigotti (1) , Aude de Gassart (1) , Carina Pforr (1) , Florencia Cano (2) , Prudence N'Guessan (1) , Alexis Combes (1) , Voahirana Camossetto (1) , Paul Lehner (3) , Evelina Gatti (1) , Philippe Pierre (1) , Angelis Rigotti (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 Addenbrookes Hospital
3 CIREL - Centre Interuniversitaire de Recherche en Education de Lille - ULR 4354

Given the heterogeneous nature of antigens, MHC-I intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC-I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while postER intracellular transport is considered to occur by default, leading to peptide-bearing MHC-I delivery to the plasma membrane. We show here that MHC-I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues. MHC-I ubiquitination is mediated by the E3 ligase MARCH9 and allows MHC-I access to syntaxin 6 (Stx6)positive endosomal compartments. We further show that MARCH9 can also target the human MHC I-like lipid antigen presentation molecule CD1a. MARCH9 expression is modulated by microbial patterns exposure in dendritic cells (DC), thus revealing the role of this ubiquitin E3 ligase in coordinating MHC-I access to endosomes and DC activation for efficient antigen cross-presentation.

Mots clés: ubiquitin ligase; HLA; antigen presentation; dendritic cells

Domaines: Sciences du Vivant [q-bio]

Francesca de Angelis Rigotti, Aude de Gassart, Carina Pforr, Florencia Cano, Prudence N'Guessan, et al.. MARCH9‐mediated ubiquitination regulates MHC I export from the TGN. Immunology and Cell Biology, 2017, 95 (9), pp.753-764. ⟨10.1038/icb.2017.44⟩. ⟨hal-03545441⟩