Human natural killer cell ontogeny, specificity and receptors

L. Moretta, E. Ciccone, M. C. Mingari, A. Moretta

Research output: Contribution to journalArticle

Abstract

Several of the generally accepted ideas on natural killer (NK) cells have been challenged by considerable experimental data that have substantially changed our view on these cells. Although maturation of NK cells can occur in the absence of a functional thymus, clonogenic precursors capable of differentiating into mature CD3-16+56+ NK cells were found in CD3-4-8-16- populations isolated from human postnatal thymus. Analysis of the cytolytic activity of interleukin 2-activated NK cell populations and clones revealed that they can lyse normal cells (e.g. phytohaemagglutinin induced blasts) isolated from some individuals. NK clones isolated from single donors displayed different patterns of cytolytic activity against a panel of allogeneic cells, thus indicating that an NK cell repertoire exists. Genetic analyses of the determinants of susceptibility/resistance to lysis together with the use of human histocompatibility leukocyte antigens (HLA)-defective variants or HLA-transfectants revealed that 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 recognise class I alleles. New monoclonal antibodies (moAb) directed to members of a novel family of NK-specific p58 molecules allowed the identification of the putative NK receptors for 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 recognised. In addition, anti-p58 moAb restored the NK-mediated lysis of class I-protected cells. A similar effect was obtained with anti-p58-induced modulation of p58 surface molecules. The role of these receptor/ligand interactions in the NK cell physiology is discussed.

Original languageEnglish
Pages (from-to)436-445
Number of pages10
JournalFORUM - Trends in Experimental and Clinical Medicine
Volume4
Issue number4
Publication statusPublished - 1994

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Keywords

  • MHC class I
  • NK cells
  • NK receptors

ASJC Scopus subject areas

  • Medicine(all)

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