T cell nature and heterogeneity of recognition structures of human natural killer (NK) cells.

Very low doses of trypsin (5 micrograms/ml) are sufficient to ablate NK cell activity. This finding was used to make several observations, and we have attempted to relate these observations to specific cell surface macromolecules. First, trypsinized effector cells no longer lysed seven different NK-susceptible targets, but the lysis of three additional targets was unaffected. These results suggest a heterogeneity of recognition potential that is inconsistent with the notion that there is only one class of NK "receptors" and one class of "target structures." Trypsin does not affect the conjugation of effector and target cells. Secondly, we have tried to identify those cell surface molecules that are affected by this low dose of enzyme. The examination of the 125I-labeled glycoprotein fraction NK-enriched cells showed that at least four molecules are cleaved, one of which may be in the T200 family. The examination of the [3H]galactose-labeled cell surface glycoproteins suggested in particular that some high m.w. glycoproteins were affected at the dose of trypsin that ablates NK function. Analysis of those molecules that we previously implicated in NK function, defined by monoclonal antibodies that block NK lysis, allowed us to rule out a role for the Tp 50 and Lp95-150 structures, while providing additional evidence of a role for the T200 glycoproteins in the trypsin-sensitive stage of cytolysis. Finally, closer examination of the electrophoretic mobilities and trypsin sensitivity of the T200 structures on highly enriched NK cells showed these structures to be indistinguishable from the T cell form of T200, yet quite distinct from the monocyte form. These results are therefore consistent with the possibility that NK cells are of the T rather than the monocyte lineage, and furthermore support a role for the T200 structure in the post-binding trypsin-sensitive stage of the NK cytolytic process.