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 + abT cell responses against viral and bacterial peptides. MICA is a highly polymor-phic ligand for NKG2D activating NK and costimulating CD8 + T cells and a ligand for tissue-resident Vd1 cd T subsets. More intriguing is the role of EPCR, a key regulator of coagulation, as a ligand for a circulating subset of Vd2 À cd 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.
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Pierre-Jean Gavlovsky, Pierre Tonnerre, Christophe Guitton, Béatrice Charreau. Expression of MHC class I-related molecules MICA, HLA-E and EPCR shape endothelial cells with unique functions in innate and adaptive immunity. Human Immunology, Elsevier, 2016, 77 (11), pp.1084-1091. ⟨10.1016/j.humimm.2016.02.007⟩. ⟨inserm-02153131⟩

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