RECOGNITION OF VIRUS-INFECTED CELLS BY NATURAL-KILLER-CELL CLONES IS CONTROLLED BY POLYMORPHIC TARGET-CELL ELEMENTS

Natural killer (NK) cells provide a first line of defense against vira l infections. The mechanisms by which NK cells recognize and eliminate infected cells are still largely unknown. To test whether target cell elements contribute to NK cell recognition of virus-infected cells, h uman NK cells were cloned from two unrelated donors and assayed for th eir ability to kill normal autologous or allogeneic cells before and a fter infection by human herpesvirus 6 (HHV-6), a T-lymphotropic herpes virus. Of 132 NK clones isolated from donor 1, all displayed strong cy tolytic activity against the NK-sensitive cell line K562, none killed uninfected autologous T cells, and 65 (49%) killed autologous T cells infected with HHV-6. A panel of representative NK clones from donors 1 and 2 was tested on targets obtained from four donors. A wide heterog eneity was observed in the specificity of lysis of infected target cel ls among the NK clones. Some clones killed none, some killed only one, and others killed more than one of the different HHV-6-infected targe t cells. Killing of infected targets was not due to complete absence o f class I molecules because class I surface levels were only partially affected by HHV-6 infection. Thus, target cell recognition is not con trolled by the effector NK cell alone, but also by polymorphic element s on the target cell that restrict NK cell recognition. Furthermore, N K clones from different donors display a variable range of specificiti es in their recognition of infected target cells.