Human NK cells and their receptors.
The past decade has witnessed important progress in our understanding of how natural killer (NK) cells function. This is primarily consequent to the identification and functional characterization of MHC-specific inhibitory receptors that allow NK cells to discriminate between normal cells and potentially harmful cells that have lost or express insufficient amounts of MHC class I molecules. More recently, a number of activating receptors or coreceptors have been identified that are involved in the process of natural cytotoxicity but may also play a role in the direct recognition of pathogen-associated structures. Surprisingly, none of the triggering receptors identified in NK cells appears to be involved in the "NK-like activity" of a subset of CD8(+) cytolytic T lymphocytes. In this case, lysis of NK-susceptible tumor target cells is the result of the TCR alpha/beta-mediated recognition of HLA-E. The potent cytolytic activity of NK cells as well as their unique mode of functioning may be exploited in therapy. An important breakthrough is the recent report that "alloreactive" NK cells, generated in haploidentical bone marrow transplantation in patients with acute myeloid leukemias, may efficiently prevent leukemic relapses as well as graft rejection and graft-vs.-host disease. This may lead to a true revolution in bone marrow transplantation, based on the exploitation of appropriate HLA-Cl I mismatches that can put NK cells in action.
Moretta
Lorenzo
L
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy. lorenzomoretta@ospedale-gaslini.ge.it
Biassoni
Roberto
R
Bottino
Cristina
C
Cantoni
Claudia
C
Pende
Daniela
D
Mingari
Maria Cristina
MC
Moretta
Alessandro
A
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; C084093:CD244 protein, human; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family