Human natural killer cells: Origin, receptors, function, and clinical applications

Lorenzo Moretta, Elisa Montaldo, Paola Vacca, Genny Del Zotto, Francesca Moretta, Pietro Merli, Franco Locatelli, Maria Cristina Mingari

Research output: Contribution to journalArticlepeer-review


Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ + T cells-both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6-to 8-week interval required for the generation of alloreactive NK cells from HSC.

Original languageEnglish
Pages (from-to)253-264
Number of pages12
JournalInternational Archives of Allergy and Immunology
Issue number4
Publication statusPublished - Nov 7 2014


  • Activating NK receptors
  • Haploidentical hematopoietic stem cell transplantation
  • Killer Ig-like receptors
  • Natural killer cells
  • NK-tumor cell interactions

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)


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