Role of HLA-G versus HLA-E on NK function: HLA-G is able to inhibit NK cytolysis by itself.

Recent studies have shown that endogenous HLA-E molecules are stabilized on the cell surface upon the expression of HLA-G which contains within its leader sequence, a nonapeptide capable of binding with the HLA-E/beta2m complex. Since HLA-E was found to be the major ligand for the CD94/NKG2A inhibitory receptor, we determined the role of HLA-G versus HLA-E on NK lysis inhibition. We showed that K562 cells transfected with HLA-G1 cDNA are protected from NK lysis by direct interaction between HLA-G1 and killing inhibitory receptor(s). This NK lysis inhibition is not dependent on HLA-E expression, since no HLA-E protein was detected on K562 cells; HLA-G1 is therefore able to inhibit NK lysis by itself.