The role of peptide presentation in the physiological function of HLA-G

The HLA-G gene gives rise to six differently spliced mRNAs. The membrane bound HLA-G1 molecule containing all three extracellular domains presents peptides that follow motif requirements similar to those of classical HLA class I molecules. This isoform is also capable of inhibiting Natural Killer (NK) cells, but is only efficiently transported to the cell surface when peptides are provided in the endoplasmic reticulum. In the absence of sufficient peptide supply to the ER a small molecule of 18-kDa is transported to the cell surface in HLA-G transfectants of LCL721.221 cells. HLA-G transfectants with impaired ER peptide supply are nevertheless protected from NK lysis.