Normal Epithelial Cells Modulating HLA Class I Surface Molecules Are Susceptible to Lysis Mediated by CD3+and CD3−“Nonspecific” Killer Cells

Natural killer (NK) cells and NK-like T cells have been described as efficiently lysing neoplastic cells derived from hematopoietic tumors. By modulating the expression of HLA class I surface molecules on normal epithelial cells, we also observed that nonneoplastic cells can efficiently be lysed by “nonspecific” effectors. Clonal analysis clearly demonstrates that the presence of HLA-specific inhibitory NK receptors, such as CD94, CD158a, and CD158b, described on NK cells, is responsible for the inhibitory signal. Thus, NK cells, as well as NK-like T cells, in the absence of HLA surface molecules on normal target cells, efficiently lyse epithelial cells.