LAG-3 DOES NOT DEFINE A SPECIFIC MODE OF NATURAL KILLING IN HUMAN

LAG-3 is a gene localized on the band p13 of human chromosome 12, clos e to the NK gene complex (NKC), expressed on activated NK cells and en coding a receptor for MHC class II molecules. Recently, LAG-3 has been proposed to define a specific mode of natural killing in mice. The pu tative role of LAG3 on human natural killer cytotoxicity has been exam ined with specific monoclonal antibodies and a recombinant soluble for m of LAG-3. Neither the antibodies, which are able to block the intera ction with the ligand, nor the recombinant product, which has retained its binding capacity for MHC class II, had an effect on the natural k illing of various target cells. Furthermore, in redirected killing ass ays, none of these antibodies were able to modulate either positively or negatively the cytotoxicity. Taken together, these data show that L AG3 has no transducing activity involved in NK cytotoxicity, ruling ou t the existence of a specific mode of natural killing defined by this molecule in humans. (C) 1998 Elsevier Science B.V. All rights reserved .