NK cell lineage and target specificity: a unifying concept

Natural killer (NK) cells play a part in tumor resistance, host immunity to viral and other microbial infections, and the regulation of lymphoid and other haemopoietic cell populations(1). Yet the lineage to which NK cells belong, and the nature of their target cell specificity remain uncertain. The phenotypic heterogeneity of cells with spontaneous cytotoxicity has led to the suggestion that NK activity is not restricted to a single cell type but is a property of cells of several different lineages at particular stages of maturation or activation. Do NK cells, like T and B lymphocytes, recognize their targets via clonally distributed receptors for distinct cell-surface antigens, or do they, like macrophages, bind to target cells via non-specific structures such as Fc receptors, complement receptors, or lectin-like receptors for ubiquitous cell-surface carbohydrates? Joseph Kaplan has previously proposed(2) that both the nature and specificity of NK cells can be accounted for in terms of a single unifying concept - that NK cells are pre-thymic T cells which, as originally proposed by Jerne(3), express germ line V gene-encoded receptors for either self or non-self histocompatibility antigens. Here he discusses how this hypothesis fits with current evidence concerning NK cell lineage and target specificity.