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Major histocompatibility complex, class I, E
PDB rendering based on 1kpr.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols HLA-E ; EA1.2; EA2.1; HLA-6.2; MHC; QA1
External IDs OMIM143010 MGI95957 HomoloGene134018 GeneCards: HLA-E Gene
RNA expression pattern
PBB GE HLA-E 200904 at tn.png
PBB GE HLA-E 200905 x at tn.png
PBB GE HLA-E 217456 x at tn.png
More reference expression data
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:
30.46 – 30.46 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.[1] 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.


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.[2]


HLA-E has a very specialized role in cell recognition by natural killer cells (NK cells).[3] HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G.[4] These peptides are released from the membrane of the endoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolic proteasome.[5][6] 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.[7] 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.[3] When CD94/NKG2A or CD94/NKG2B is stimulated, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis. However, when CD94/NKG2C is stimulated an activating effect on the NK cell is observed.


  1. ^ 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". J Immunol 140 (11): 4024–30. PMID 3131426. 
  2. ^ "Entrez Gene: HLA-E major histocompatibility complex, class I, E". 
  3. ^ 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. (June 1998). "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C". Nature 391 (6669): 795–9. doi:10.1038/35869. PMID 9486650. 
  4. ^ Braud V, Jones EY, McMichael A (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". Eur. J. Immunol. 27 (5): 1164–9. doi:10.1002/eji.1830270517. PMID 9174606. 
  5. ^ Lemberg MK, Bland FA, Weihofen A, Braud VM, Martoglio B (December 2001). "Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes". J. Immunol. 167 (11): 6441–6. doi:10.4049/jimmunol.167.11.6441. PMID 11714810. 
  6. ^ Bland FA, Lemberg MK, McMichael AJ, Martoglio B, Braud VM (September 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". J. Biol. Chem. 278 (36): 33747–52. doi:10.1074/jbc.M305593200. PMID 12821659. 
  7. ^ Braud VM, Allan DS, Wilson D, McMichael AJ. (1998). "TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide". Curr. Biol. 8 (1): 1–10. doi:10.1016/S0960-9822(98)70014-4. PMID 9427624. 

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". Eur. J. Immunol. 32 (5): 1205–11. doi:10.1002/1521-4141(200205)32:5<1205::AID-IMMU1205>3.0.CO;2-Y. PMID 11981807. 
  • Jensen PE, Sullivan BA, Reed-Loisel LM, Weber DA (2004). "Qa-1, a nonclassical class I histocompatibility molecule with roles in innate and adaptive immunity". Immunol. Res. 29 (1-3): 81–92. doi:10.1385/IR:29:1-3:081. PMID 15181272.