HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN (HLA)-G MOLECULES INHIBIT NKAT3 EXPRESSING NATURAL-KILLER-CELLS

The crucial immunological function of the classical human major histoc ompatibility complex (MHC) class I molecules, human histocompatibility leukocyte antigen (HLA)-A, -B, and -C, is the presentation of peptide s to T cells. A secondary function is the inhibition of natural killer (NK) cells, mediated by binding of class I molecules to NK receptors. In contrast, the function of the nonclassical human MHC class I molec ules, HLA-E, -F, and -G, is still a mystery. The specific expression o f HLA-G in placental trophoblast suggests an important role for this m olecule in the immunological interaction between mother and child. The fetus, semiallograft by its genotype, escapes maternal allorecognitio n by downregulation of HLA-A and HLA-B molecules at this interface. It has been suggested that the maternal NK recognition of this downregul ation is balanced by the expression of HLA-G, thus preventing damage t o the placenta. Here, we describe the partial inhibition of NK lysis o f the MHC class I negative cell line LCL721.221 upon HLA-G transfectio n. We present three NK lines that are inhibited via the interaction of their NKAT3 receptor with HLA-G and with HLA-Bw4 molecules. Inhibitio n can be blocked by the anti-NKAT3 antibody 5.133. In conclusion, NK i nhibition by HLA-G via NKAT3 may contribute to the survival of the fet al semiallograft in the mother during pregnancy.