HLA-G2,-G3, and-G4 isoforms expressed as nonmature cell surface glycoproteins inhibit NK and antigen-specific CTL cytolysis

HLA-G is a nonclassical MHC class I molecule that plays a major role in mat ernal-fetal tolerance. Four membrane-bound (HLA-G1 to -G4) and two soluble (HLA-G5, and -G6) proteins are generated by alternative splicing. Only HLA- GI has been extensively studied in terms of both expression and function. W e provide evidence here that HLA-G2, -G3, and -G4 truncated isoforms reach the cell surface of transfected cells, as endoglycosidase H-sensitive glyco proteins, after a 2-h chase period. Moreover, cytotoxicity, experiments sho w that these transfected cells are protected from the lytic activity of bot h innate (NK cells) and acquired (CTL) effectors. These findings highlight the immunomodulatory role that HLA-G2, -G3, and -G4 proteins will assume du ring physiologic or pathologic processes in which HLA-G1 expression is alte red. The Journal of Immunology, 2001.