HLA-E

Major histocompatibility complex, class I, E
250px PDB rendering based on 1kpr.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1KPR, 1KTL, 1MHE, 2ESV, 3AM8, 3BZE, 3BZF, 3CDG, 3CII
Identifiers
Symbols	HLA-E ; EA1.2; EA2.1; HLA-6.2; MHC; QA1
External IDs	OMIM: 143010 MGI: 95957 HomoloGene: 134018 GeneCards: HLA-E Gene
Gene ontology Molecular function • receptor binding • beta-2-microglobulin binding • MHC class I protein binding • peptide antigen binding • natural killer cell lectin-like receptor binding Cellular component • Golgi membrane • plasma membrane • cell surface • ER to Golgi transport vesicle membrane • phagocytic vesicle membrane • early endosome membrane • MHC class Ib protein complex • MHC class I protein complex • extracellular exosome • integral component of lumenal side of endoplasmic reticulum membrane Biological process • positive regulation of T cell mediated cytotoxicity • adaptive immune response • antigen processing and presentation of peptide antigen via MHC class I • antigen processing and presentation of endogenous peptide antigen via MHC class Ib • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent • regulation of natural killer cell mediated immunity • positive regulation of natural killer cell mediated immunity • cytokine-mediated signaling pathway • antibacterial humoral response • positive regulation of interleukin-13 production • positive regulation of interleukin-4 production • positive regulation of TRAIL production • positive regulation of tumor necrosis factor production • CD8-positive, alpha-beta T cell activation • protection from natural killer cell mediated cytotoxicity • antigen processing and presentation of exogenous peptide antigen via MHC class I • innate immune response • regulation of immune response • defense response to Gram-positive bacterium • positive regulation of immunoglobulin secretion • interferon-gamma-mediated signaling pathway • type I interferon signaling pathway • positive regulation of CD8-positive, alpha-beta T cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE HLA-E 200904 at tn.png
File:PBB GE HLA-E 200905 x at tn.png
File:PBB GE HLA-E 217456 x at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3133	15040
Ensembl	ENSG00000204592	ENSMUSG00000067212
UniProt	P13747	P06339
RefSeq (mRNA)	NM_005516	NM_010398
RefSeq (protein)	NP_005507	NP_034528
Location (UCSC)	Chr 6: 30.49 – 30.49 Mb	Chr 17: 36.03 – 36.03 Mb
PubMed search	[1]	[2]

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. 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.

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.

Function

HLA-E has a very specialized role in cell recognition by natural killer cells (NK cells). HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G. These peptides are released from the membrane of the endoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolic proteasome. 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. 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. 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.

Further reading

• Kuby Immunology, 6th edition, by Thomas J. Kindt, Richard A. Goldsby,and Barbara A.Kuby W.H. Freeman and Company,New York