title: Expression of MHC class I-related molecules MICA, HLA-E and EPCR shape endothelial cells with unique functions in innate and adaptive immunity.
abstract: Endothelial cells (ECs) located at the interface of blood and tissues display regulatory activities toward coagulation, inflammation and vascular homeostasis. By expressing MHC class I and II antigens, ECs also contribute to immune responses. In transplantation, graft ECs are both trigger and target of alloimmune responses. ECs express a set of MHC class I-like or structural related molecules such as HLA-E, MHC class I related chain A (MICA) and the endothelial protein C receptor (EPCR) that provide multiple and unique functions to ECs. HLA-E is a low polymorphic ligand for the CD94/NKG2A/C receptors, and triggers HLA-E-restricted CD8+αβT cell responses against viral and bacterial peptides. MICA is a highly polymorphic ligand for NKG2D activating NK and costimulating CD8+T cells and a ligand for tissue-resident Vδ1 γδ T subsets. More intriguing is the role of EPCR, a key regulator of coagulation, as a ligand for a circulating subset of Vδ2-γδ T cells. Coexpression of this set of MHC class I-related molecules that allow ECs to activate a subtle array of immune responses upon stress and infection may also influence transplant outcome. Here, the respective structure, expression, and functions of HLA-E, MICA and EPCR as well as the impact of their polymorphism are reviewed.
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, Nantes F44000, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN, Nantes F44000, France; LUNAM Université de Nantes, Faculté de Médecine, Nantes F44000, France; IHU-CESTI, Nantes F44000, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Gavlovsky
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, Nantes F44000, France; LUNAM Université de Nantes, Faculté de Médecine, Nantes F44000, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tonnerre
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, Nantes F44000, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN, Nantes F44000, France; LUNAM Université de Nantes, Faculté de Médecine, Nantes F44000, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Guitton
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, Nantes F44000, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN, Nantes F44000, France; LUNAM Université de Nantes, Faculté de Médecine, Nantes F44000, France. Electronic address: Beatrice.Charreau@univ-nantes.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
mesh_terms: D056704:Adaptive Immunity; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D042783:Endothelial Cells / Q000276:immunology*; D000074283:Endothelial Protein C Receptor; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D059467:Transcriptome; D000097625:HLA-E Antigens
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D015395:Histocompatibility Antigens Class I; D011956:Receptors, Cell Surface; D000097625:HLA-E Antigens; C099187:MHC class I-related chain A; C478370:PROCR protein, human
keywords: EPCR; Endothelial cells; HLA-E; MHC; MICA