HLA-E — Major histocompatibility complex, class I, E

HLA-E belongs to a gene co-expression module in 13 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.

HLA-E's module in each cell type

About the gene

Function

Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination. In complex with B2M/beta-2-microglobulin binds nonamer self-peptides derived from the signal sequence of classical MHC class Ia molecules (VL9 peptides - VMAPRT[V/L][L/V/I/F]L). Peptide-bound HLA-E- B2M heterotrimeric complex primarily functions as a ligand for natural killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK cells to monitor the expression of other MHC class I molecules in healthy cells and to tolerate self. Upon cellular stress, preferentially binds signal sequence-derived peptides from stress- induced chaperones and is no longer recognized by NK cell inhibitory receptor KLRD1-KLRC1, resulting in impaired protection from NK cells. Binds signal sequence-derived peptides from non- classical MHC class Ib HLA-G molecules and acts as a ligand for NK cell activating receptor KLRD1-KLRC2, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal- fetal tolerance during pregnancy. Besides self-peptides, can also bind and present pathogen-derived peptides conformationally similar to VL9 peptides to alpha-beta T cell receptor (TCR) on unconventional CD8-positive cytotoxic T cells, ultimately triggering antimicrobial immune response. Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant KALGPAATL epitopes) predominantly to CD8-positive T cell clones expressing a TRAV17-containing TCR, triggering HLA-E-restricted T cell responses. Presents mycobacterial peptides to HLA-E- restricted CD8-positive T cells eliciting both cytotoxic and immunoregulatory functions. (Microbial infection) Viruses like human cytomegalovirus have evolved an escape mechanism whereby virus-induced down-regulation of host MHC class I molecules is coupled to the binding of viral peptides to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK cell immune tolerance to infected cells. (Microbial infection) May bind HIV-1 gag/Capsid protein p24- derived peptide (AISPRTLNA) on infected cells and may inhibit NK cell cytotoxicity, a mechanism that allows HIV-1 to escape immune recognition. (Microbial infection) Upon SARS-CoV-2 infection, may contribute to functional exhaustion of cytotoxic NK cells and CD8- positive T cells. 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

Human Protein Atlas · Open Targets · UniProt

Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.