HLA-E

HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a is_associated_with::protein that in humans is encoded by the HLA-E is_associated_with::gene. The human HLA-E is a non-classical is_associated_with::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 is_associated_with::Qa-1b.

Structure
Like other is_associated_with::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 is_associated_with::exons. Exon one encodes the is_associated_with::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 is_associated_with::transmembrane domain, and exons 6 and 7 encode the cytoplasmic tail.

Function
HLA-E has a very specialized role in cell recognition by is_associated_with::natural killer cells (NK cells). HLA-E binds a restricted subset of peptides derived from is_associated_with::signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G. These peptides are released from the membrane of the is_associated_with::endoplasmic reticulum (ER) by the is_associated_with::signal peptide peptidase and trimmed by the cytosolic is_associated_with::proteasome. Upon transport into the ER lumen by the is_associated_with::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 is_associated_with::CD94/is_associated_with::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.