From the Ludwig Institute. for Cancer Resesarch, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland though NK cells and T cells share a number of biological functions including cytotoxicity and lymphokine secretion (1), they appear to differ fundamentally in the structure of their antigen receptors. Whereas T cells are known to recognize foreign antigens via their CD3-associated heterodimeric ce/15 or 3'/g TCK, the antigen recognition structures used by NK cells are still in the process of being ducidated. In this respect, current evidence (2-5) suggests that NK cells express polymorphic (but nonrearranging) receptors that bdoug to the NKR-Pl and Ly-49 families in mouse and the recently doned p58 family in humans. The nature of the ligands recognized by NK cells is controversial, although there is functional evidence that both Ly-49 and p58 receptor families may mediate negative signals upon engagement of particular MHC class I alleles (2-5). In contrast, NKK-Pl receptors appear to bind to a heterogeneous group of carbohydrate ligands (6), thereby triggering effector functions such as cytolysis (6, 7).

NK and T cells probably arise from related but distinct developmental lineages (8). Whereas the majority of ce//3 or~///~ T cells depend upon the thymus for their development, NK cells develop normally in athymic (nude) mice. Furthermore, recombination-deficient mutant (RAG-/-or SCID) mice have normal levels of NK cells despite the complete absence of ce/B or" y//~ T cells. Nevertheless, it is likely that both NK and T cells arise from a common" lymphoid committed" precursor cell, since both lineages (as weU as B cells) are absent in mice lacking the ikaros transcription factor, whereas other hematopoietic cells develop normally in these mutant mice (9).