Recombinant Human HLA class I histocompatibility antigen, alpha chain E (HLA-E), partial

Function

(Microbial infection) Upon SARS-CoV-2 infection, may contribute to functional exhaustion of cytotoxic NK cells and CD8-positive T cells (PubMed:32859121). Binds SARS-CoV-2 S/Spike protein S1-derived peptide (LQPRTFLL) expressed on the surface of lung epithelial cells, inducing NK cell exhaustion and dampening of antiviral immune surveillance (PubMed:32859121)

Subcellular Location

Secreted

Tissue Specificity

Expressed in secretory endometrial cells during pregnancy (at protein level). The expression in nonlymphoid tissues is restricted to endothelial cells from all types of vessels, including arteries, veins, capillaries, and lymphatics (at protein level). In lymphoid organs, it is mainly expressed in endothelial venules, B and T cells, monocytes, macrophages, NK cells and megakaryocytes (at protein level)

Subunit

Forms a heterotrimer with B2M and a self- or a pathogen-derived peptide (peptide-bound HLA-E-B2M) (PubMed:18339401, PubMed:30087334, PubMed:35705051). Similarly to MHC class Ia assembly, HLA-E-B2M heterodimer interacts with components of the antigen processing machinery TAPBP and TAP1-TAP2 complex; this interaction is required for peptide loading and translocation to the cell surface (PubMed:9427624). Interacts with CALCR; this interaction is required for appropriate folding (PubMed:9427624). The optimum binding peptide is a nonamer (VL9) that is primarily derived from amino-acid residues 3-11 of the signal sequences of most HLA-A, -B, -C and -G molecules (PubMed:18083576, PubMed:18339401, PubMed:9660937, PubMed:9754572). The VL9 peptide anchors to five main sites in the peptide-binding groove of HLA-E (PubMed:18339401). Peptide-bound HLA-E-B2M complex interacts with KLRD1-KLRC1 receptor on NK cells (PubMed:18083576, PubMed:9486650). Binds with lower affinity to activating KLRD1-KLRC2 (PubMed:18083576, PubMed:23335510). The common subunit KLRC1 plays a prominent role in directly interacting with HLA-E (PubMed:18083576). Peptide-bound HLA-E-B2M interacts with the alpha-beta TCR on unconventional CD8+ T cells (PubMed:16474394). Peptide-free HLA-E interacts with HLA-F-B2M complex; this interaction may regulate the intracellular trafficking and the stability of peptide-free MHC class I open conformers (OCs)

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