ONTOGENY, SPECIFIC FUNCTIONS AND RECEPTORS OF HUMAN NATURAL-KILLER-CELLS

Several of the generally accepted ideas on natural killer (NK) cells h ave been challenged by recent data that have substantially modified ou r view on these lymphoid cell populations. Although maturation of NK c ells can occur in the absence of a functional thymus, clonogenic precu rsors capable of differentiating into mature CD3(-)16(+)56(+) NK cells were found in CD3(-)4(-)s(-)16(-) populations isolated from human pos tnatal thymus. Analysis of the cytolytic activity of interleukin-2-act ivated NK cell populations and clones revealed that they can lyse norm al cells (e.g., PHA blasts) isolated from certain individuals. In addi tion, NK clones isolated from single donors displayed different patter ns of cytolytic activity against a panel of allogeneic cells, thus ind icating that an NK cell repertoire exists. Genetic analyses of the det erminants responsible for susceptibility/resistance to lysis together with the use of HLA-defective variants or HLA-transfectants revealed t hat the expression of given HLA class I alleles protects target cells from lysis by different groups of NK clones. Thus, NK cells express a clonally distributed ability to recognize HLA class I alleles. New mon oclonal antibodies directed to members of a novel family of NK-specifi c p58 molecules allowed identification of the putative NK receptors fo r different major histocompatibility complex class I alleles. Indeed, a precise correlation has been established between expression of given p58 molecules (e.g., EB6 and GL183 molecules) and class I alleles rec ognized. In addition, anti-p58 monoclonal antibodies restored the NK-m ediated lysis of class I-protected cells. A similar effect was obtaine d with anti-p58-induced modulation of p58 surface molecules. The physi ological implications of these receptor-ligand interactions are discus sed.