 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.