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Specific functions of human NK cells.

E Ciccone1, A Moretta, L Moretta

  • 1Istituto Nazionale per la Ricerca sul Cancro, Genua, Italy.

Immunology Letters
|February 1, 1992
PubMed
Summary

Natural killer (NK) cells can specifically recognize and lyse allogeneic cells, challenging previous assumptions. This recognition is mediated by clonally distributed receptors, identified as novel 58-kDa surface molecules.

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Area of Science:

  • Immunology
  • Cellular immunology
  • NK cell biology

Background:

  • Natural killer (NK) cells were traditionally considered antigen-non-specific due to the absence of CD3/TCR and surface Ig.
  • Recent findings suggest NK cells may possess antigen-recognition capabilities.

Purpose of the Study:

  • To investigate the antigen-recognition potential of NK cells.
  • To characterize the specificities and inheritance patterns of NK cell-mediated lysis.
  • To identify the molecular basis of NK cell recognition.

Main Methods:

  • Mixed lymphocyte culture (MLC) assays with CD3-CD16+ cells and allogeneic mononuclear cells.
  • Cytotoxicity assays using cloned NK cells against tumor cells and PHA blasts.
  • Analysis of NK cell reactivity patterns and inheritance of specificities.
  • Generation and screening of monoclonal antibodies (mAbs) against NK clones.

Main Results:

  • CD3-CD16+ NK cells demonstrated specific responses in MLC and lysis of allogeneic PHA blasts.
  • NK cell recognition of normal allogeneic cells and tumor cells are distinct functions.
  • At least four distinct NK cell specificities were identified based on lysis patterns.
  • NK-defined specificities are autosomally inherited in a recessive manner and linked to chromosome 6.
  • Two mAbs, GL183 and EB6, identified a novel 58-kDa surface molecule family on NK cells.

Conclusions:

  • NK cells possess clonally distributed specificities for recognizing allogeneic cells.
  • This specific recognition is mediated by novel 58-kDa surface molecules, suggesting the existence of clonally distributed NK cell receptors.
  • The findings challenge the paradigm of NK cells as solely innate immune effectors and point towards adaptive-like features.

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