HLA-E

HLA-E
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 3CII, 1KPR, 1KTL, 1MHE, 2ESV, 3AM8, 3BZE, 3BZF, 3CDG
Identifiers
Aliases	HLA-E, EA1.2, EA2.1, HLA-6.2, MHC, QA1, major histocompatibility complex, class I, E
External IDs	OMIM: 143010; MGI: 2442805; HomoloGene: 134018; GeneCards: HLA-E; OMA:HLA-E - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p22.1 Start 30,489,509 bp[1] End 30,494,194 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B1 Start 36,420,126 bp[2] End 36,422,550 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood right lung granulocyte upper lobe of left lung monocyte spleen lymph node subcutaneous adipose tissue appendix gallbladder Top expressed in thymus intestinal villus granulocyte mesenteric lymph nodes duodenum Paneth cell jejunum zygote right kidney blastocyst More reference expression data BioGPS More reference expression data
Gene ontology Molecular function beta-2-microglobulin binding MHC class I protein binding signaling receptor binding natural killer cell lectin-like receptor binding peptide antigen binding T cell receptor binding Cellular component integral component of membrane phagocytic vesicle membrane early endosome membrane membrane MHC class Ib protein complex Golgi membrane plasma membrane cell surface MHC class I protein complex ER to Golgi transport vesicle membrane integral component of lumenal side of endoplasmic reticulum membrane extracellular exosome recycling endosome membrane Biological process antigen processing and presentation adaptive immune response antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent CD8-positive, alpha-beta T cell activation interferon-gamma-mediated signaling pathway immune system process antigen processing and presentation of peptide antigen via MHC class I positive regulation of T cell mediated cytotoxicity positive regulation of TRAIL production positive regulation of interleukin-4 production antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent protection from natural killer cell mediated cytotoxicity positive regulation of interleukin-13 production type I interferon signaling pathway immune response regulation of natural killer cell mediated immunity positive regulation of natural killer cell mediated immunity regulation of immune response positive regulation of tumor necrosis factor production innate immune response positive regulation of CD8-positive, alpha-beta T cell proliferation antigen processing and presentation of endogenous peptide antigen via MHC class Ib Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3133 667803 Ensembl ENSG00000204592 ENSG00000225201 ENSG00000236632 ENSG00000230254 ENSG00000206493 ENSG00000233904 ENSG00000229252 ENSMUSG00000073405 UniProt P13747 n/a RefSeq (mRNA) NM_005516 NM_001271005 RefSeq (protein) NP_005507 n/a Location (UCSC) Chr 6: 30.49 – 30.49 Mb Chr 17: 36.42 – 36.42 Mb PubMed search [3] [4]
Wikidata
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HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a protein that in humans is encoded by the HLA-E gene.^[5] The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is called Qa-1b, officially known as H2-T23.

Structure

Like other MHC class I molecules, HLA-E is a heterodimer consisting of an α heavy chain and a light chain (β-2 microglobulin). The heavy chain is approximately 45 kDa and anchored in the membrane. The HLA-E gene contains 8 exons. Exon one encodes the signal peptide, exons 2 and 3 encode the α1 and α2 domains, which both bind the peptide, exon 4 encodes the α3 domain, exon 5 encodes the transmembrane domain, and exons 6 and 7 encode the cytoplasmic tail.^[6]

Function

HLA-E has a very specialized role in cell recognition by natural killer cells (NK cells).^[7] HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G.^[8] These peptides are released from the membrane of the endoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolic proteasome.^[9][10] Upon transport into the ER lumen by the transporter associated with antigen processing (TAP), these peptides bind to a peptide binding groove on the HLA-E molecule.^[11] This allows HLA-E to assemble correctly and to be expressed on the cell surface. NK cells recognize the HLA-E+peptide complex using the heterodimeric receptor CD94/NKG2A/B/C.^[7] When CD94/NKG2A or CD94/NKG2B is engaged, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis. However, binding of HLA-E to CD94/NKG2C (see KLRC2) results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses,^[12] where adaptive NK cells that express CD94/NKG2C can specifically recognise HCMV-derived peptide antigens.^[13]

References

Further reading