HLA-E

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HLA-E
HLA-E.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HLA-E, EA1.2, EA2.1, HLA-6.2, MHC, QA1, major histocompatibility complex, class I, E
External IDs OMIM: 143010 MGI: 95957 HomoloGene: 134018 GeneCards: HLA-E
Gene location (Human)
Chromosome 6 (human)
Chr. Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for HLA-E
Genomic location for HLA-E
Band 6p22.1 Start 30,489,467 bp[1]
End 30,494,205 bp[1]
RNA expression pattern
PBB GE HLA-E 200905 x at fs.png

PBB GE HLA-E 217456 x at fs.png

PBB GE HLA-E 200904 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005516

NM_010398

RefSeq (protein)

NP_005507

NP_034528

Location (UCSC) Chr 6: 30.49 – 30.49 Mb Chr 6: 36.03 – 36.03 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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[edit]

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[edit]

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 inhibitory 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 results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses.[12]

References[edit]

  1. ^ a b c ENSG00000225201, ENSG00000236632, ENSG00000230254, ENSG00000206493, ENSG00000233904, ENSG00000229252 GRCh38: Ensembl release 89: ENSG00000204592, ENSG00000225201, ENSG00000236632, ENSG00000230254, ENSG00000206493, ENSG00000233904, ENSG00000229252 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000067212 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Mizuno S, Trapani JA, Koller BH, Dupont B, Yang SY (Jun 1988). "Isolation and nucleotide sequence of a cDNA clone encoding a novel HLA class I gene". Journal of Immunology. 140 (11): 4024–30. PMID 3131426. 
  6. ^ "Entrez Gene: HLA-E major histocompatibility complex, class I, E". 
  7. ^ a b Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (Feb 1998). "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C". Nature. 391 (6669): 795–9. PMID 9486650. doi:10.1038/35869. 
  8. ^ Braud V, Jones EY, McMichael A (May 1997). "The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9". European Journal of Immunology. 27 (5): 1164–9. PMID 9174606. doi:10.1002/eji.1830270517. 
  9. ^ Lemberg MK, Bland FA, Weihofen A, Braud VM, Martoglio B (Dec 2001). "Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes". Journal of Immunology. 167 (11): 6441–6. PMID 11714810. doi:10.4049/jimmunol.167.11.6441. 
  10. ^ Bland FA, Lemberg MK, McMichael AJ, Martoglio B, Braud VM (Sep 2003). "Requirement of the proteasome for the trimming of signal peptide-derived epitopes presented by the nonclassical major histocompatibility complex class I molecule HLA-E". The Journal of Biological Chemistry. 278 (36): 33747–52. PMID 12821659. doi:10.1074/jbc.M305593200. 
  11. ^ Braud VM, Allan DS, Wilson D, McMichael AJ (Jan 1998). "TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide". Current Biology. 8 (1): 1–10. PMID 9427624. doi:10.1016/S0960-9822(98)70014-4. 
  12. ^ Rölle A, Pollmann J, Ewen EM, Le VT, Halenius A, Hengel H, Cerwenka A (Dec 2014). "IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion". The Journal of Clinical Investigation. 124 (12): 5305–16. PMC 4348979Freely accessible. PMID 25384219. doi:10.1172/JCI77440. 

Further reading[edit]

  • Kuby Immunology, 6th edition, by Thomas J. Kindt, Richard A. Goldsby,and Barbara A.Kuby W.H. Freeman and Company,New York
  • Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A (May 2002). "Human natural killer cells: their origin, receptors and function". European Journal of Immunology. 32 (5): 1205–11. PMID 11981807. doi:10.1002/1521-4141(200205)32:5<1205::AID-IMMU1205>3.0.CO;2-Y. 
  • Jensen PE, Sullivan BA, Reed-Loisel LM, Weber DA (Jun 2004). "Qa-1, a nonclassical class I histocompatibility molecule with roles in innate and adaptive immunity". Immunologic Research. 29 (1–3): 81–92. PMID 15181272. doi:10.1385/IR:29:1-3:081.