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
Gene ontology Molecular function • beta-2-microglobulin binding • MHC class I protein binding • receptor binding • natural killer cell lectin-like receptor binding • peptide antigen 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 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 • antibacterial humoral response • 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 • positive regulation of immunoglobulin secretion • antigen processing and presentation of endogenous peptide antigen via MHC class Ib • defense response to Gram-positive bacterium Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3133	667803
Ensembl	n/a	n/a
UniProt	P13747	n/a
RefSeq (mRNA)	NM_005516	NM_001271005
RefSeq (protein)	NP_005507.3	n/a
Location (UCSC)	Chr 6: 30.49 – 30.49 Mb	n/a
PubMed search	[1]	[2]
Wikidata

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.^[3] 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.^[4]

Function

HLA-E has a very specialized role in cell recognition by natural killer cells (NK cells).^[5] HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G.^[6] These peptides are released from the membrane of the endoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolic proteasome.^[7][8] 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.^[9] 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 inhibitory receptor CD94/NKG2A/B/C.^[5] 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 results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses.^[10]

References

Further reading

PDB gallery
1kpr: The human non-classical major histocompatibility complex molecule HLA-E  1ktl: The human non-classical major histocompatibility complex molecule HLA-E  1mhe: THE HUMAN NON-CLASSICAL MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE HLA-E  2esv: Structure of the HLA-E-VMAPRTLIL/KK50.4 TCR complex