HLAE Antibody - #DF12002

Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination. In complex with B2M/beta-2-microglobulin binds nonamer self-peptides derived from the signal sequence of classical MHC class Ia molecules (VL9 peptides). Peptide-bound HLA-E-B2M heterotrimeric complex primarily functions as a ligand for natural killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK cells to monitor the expression of other MHC class I molecules in healthy cells and to tolerate self. Upon cellular stress, preferentially binds signal sequence-derived peptides from stress-induced chaperones and is no longer recognized by NK cell inhibitory receptor KLRD1-KLRC1, resulting in impaired protection from NK cells. Binds signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules and acts as a ligand for NK cell activating receptor KLRD1-KLRC2, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal-fetal tolerance during pregnancy. Besides self-peptides, can also bind and present pathogen-derived peptides conformationally similar to VL9 peptides to alpha-beta T cell receptor (TCR) on unconventional CD8+ cytotoxic T cells, ultimately triggering antimicrobial immune response.

(Microbial infection) Viruses like human cytomegalovirus have evolved an escape mechanism whereby virus-induced down-regulation of host MHC class I molecules is coupled to the binding of viral peptides to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK cell immune tolerance to infected cells.

N-glycosylated.

The soluble form (sHLA-E) can be partly produced by proteolytic cleavage at the cell surface (shedding) by a matrix metalloproteinase. Alternative splicing is also suggested as a mechanism for generation of sHLA-E, although it remains to be proved.

Cell membrane>Single-pass type I membrane protein. Golgi apparatus membrane.

Secreted.

Expressed in secretory endometrial cells during pregnancy (at protein level). The expression in nonlymphoid tissues is restricted to endothelial cells from all types of vessels, including arteries, veins, capillaries, and lymphatics (at protein level). In lymphoid organs, it is mainly expressed in endothelial venules, B and T cells, monocytes, macrophages, NK cells and megakaryocytes (at protein level).

Forms a heterotrimer with B2M and a self- or a pathogen-derived peptide (peptide-bound HLA-E-B2M). Similarly to MHC class Ia assembly, HLA-E-B2M heterodimer interacts with components of the antigen processing machinery TAPBP and TAP1-TAP2 complex; this interaction is required for peptide loading and translocation to the cell surface. Interacts with CALCR; this interaction is required for appropriate folding. The optimum binding peptide is a nonamer (VL9) that is primarily derived from amino-acid residues 3-11 of the signal sequences of most HLA-A, -B, -C and -G molecules. The VL9 peptide anchors to five main sites in the peptide-binding groove of HLA-E. Peptide-bound HLA-E-B2M complex interacts with KLRD1-KLRC1 receptor on NK cells. Binds with lower affinity to activating KLRD1-KLRC2. The common subunit KLRC1 plays a prominent role in directly interacting with HLA-E. Peptide-bound HLA-E-B2M interacts with the alpha-beta TCR on unconventional CD8+ T cells. Peptide-free HLA-E interacts with HLA-F-B2M complex; this interaction may regulate the intracellular trafficking and the stability of peptide-free MHC class I OCs.

Belongs to the MHC class I family.