ICAM-2 REDISTRIBUTED BY EZRIN AS A TARGET FOR KILLER-CELLS

VERY little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the in tercellular adhesion molecule ICAM-2 and is regulated by the distribut ion of ICAM-2. The level of ICAM-2 expression in NK-sensitive and resi stant cells is similar, but in sensitive cells ICAM-2 is concentrated into bud-like cellular projections known as uropods, whereas in resist ant cells it is evenly distributed. The cytoskeletal-membrane linker p rotein ezrin is also localized in uropods. Transfection of human ezrin into NK-resistant cells induces uropod formation, redistribution of I CAM-2 and ezrin, and sensitizes target cells to interleukin-2-activate d killing. These results reveal a new mechanism of target-cell recogni tion: cytotoxic cells recognize adhesion molecules that are already pr esent on normal cells, but in diseased cells are concentrated into a b iologically active cell-surface region by cytoskeletal reorganization. The results also highlight the importance of cytoskeletal interaction s in the regulation of ICAM-2-mediated adhesive phenomena.