Target-effector interaction in the human and murine natural killer system: specificity and xenogeneic reactivity of the solubilized natural killer-target structure complex and its loss in a somatic cell hybrid.

Abstract

Pre-incubation of natural killer (NK) cells with electrophoresis purified proteins from a variety of NK-sensitive murine and human tumor cells specifically prevented subsequent binding to the intact, homologous target cell. The NK-target structures (NK-TS) consisted of some or all of 4 characteristic molecular species, tentatively assigned MW of 140 K [140,000], 160 K, 190 K and 240 K (.+-. 10 K) based on electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels. When these NK-TS molecules were compared in cross-inhibition assays, the large 240 K molecule most often carried the unique NK specificity whereas the smaller 140 K molecules cross-reacted between YAC [Moloney virus-induced lymphoma], 136-6 [lymphoma] and X-63 [plasmacytoma] in the mouse and between Molt-4 [neoplastic peripheral leukocytes] and K562 [neoplastic pleural effusion] in the human. Mouse NK cells recognized a different spectrum of NK-TS molecules than human NK cells. The control of NK-TS expression was partially revealed in a cloned, somatic cell hybrid between an NK sensitive (YAC-IR [lymphoma]) and insensitive (A9HT [mouse leukemia]) cell line. The hybrid did not express NK-TS and did not bind to NK cells which is in accordance with negative NK cytolytic results previously reported. Although unique specificities are carried by some of the multiple NK-TS protein molecules, cross-reactions were widespread. The NK cell may be polyspecific and may have some heterogeneity in the recognition structure although much less than would be expected of an antibody-combining site.