Origin and functions of human natural killer cells
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Recent data have substantially modified our view of natural killer cells. Although maturation of natural killer cells occurs in the absence of a functional thymus, we have shown that clonogenic precursors capable of differentiating into mature CD3−16+56+ natural killer cells exist in CD3−4−8−16− populations isolated from human thymus. Analysis of peripheral bloodderived natural killer clones showed that they can lyse normal cells (e.g., phytohemagglutinin-induced blasts) isolated from some individuals. Importantly, natural killer clones isolated from single individuals displayed different patterns of cytolytic activity against a panel of normal allogeneic cells. These data suggested the existence of a natural killer cell repertoire. A number of observations have revealed that the expression of given HLA class I alleles protects target cells from lysis by different groups of natural killer clones. Evidence has been gained by genetic analysis of the determinants responsible for susceptibility/resistance to lysis by natural killer clones together with analysis, as target cells, of HLA-defective variants or HLA transfectants. Thus, natural killer cells were found to express a clonally distributed ability to recognize HLA class I alleles. The selection of new monoclonal antibodies directed against members of a novel family of natural killer specific p58 molecules allowed the identification of the putative natural killer receptors for different MHC class I alleles. Firstly, a correlation was established between the expression of given p58 molecules (e.g., EB6 and GL183) and the class I alleles recognized. Secondly, anti-p58 monoclonal antibodies restored the natural killer-mediated lysis of class I-protected cells. A similar effect was obtained by inducing modulation of p58 surface molecules with anti-p58 monoclonal antibodies. The implications of these receptor/ligand interactions in the physiopathological behavior of natural killer cells are discussed.
Key wordsNatural killer cells Natural killer receptors MHC class I Natural killer repertoire
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