The HLA-G*0105N null allele induces cell surface expression of HLA-E molecule and promotes CD94/NKG2A-mediated recognition in JAR choriocarcinoma cell line

HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast cells, and is thought to play a key role in the induction of maternofetal tolerance during pregnancy. In addition, the HLA-G gene provides a suitable leader sequence peptide capable of binding to HLA-E. However, the existence of placentas homozygous for the HLA-G*0105N null allele suggests that HLA-G1 might not be essential for fetal survival. To investigate whether expression of the HLA-G* 0105N allele supports HLA-E cell surface expression, we transfected the HLA-G* 0105N gene into JAR trophoblast cells. Flow cytometry analysis showed that HLA-G* 0105N-transfected cells express surface HLA-E to a similar extent as the unmutated HLA-G gene, whereas HLA-G1 cell surface expression was undetectable. Using the NKL cell line in a standard Cr-51 release assay, the HLA-E molecules were found to inhibit natural killer lysis, through a mechanism partially dependent on CD94/NKG2A-mediated recognition.