Regulation of myeloid cell proliferation and survival by p75/AIRM1 and CD33 surface receptors
Major progresses have recently been made toward a better understanding of the molecular mechanisms regulating the NK cell function. This is primarily the result of the discovery of a number of receptors which regulate the NK cell function. Thus, the identification of various MHC-class I-specific inhibitory NK receptors (iNKR) revealed a sophisticated capability of discriminating between normal and tumor (or virally-infected) cells (1-4). All iNKR are characterized by the presence of an immunoreceptor tyrosine-based inhibition motif (ITIM) in their cytoplasmic tail (3-6). The surface expression of iNKR that inhibit the NK-cell function, explains why NK cells lyse only those target cells that have lost or express insufficient amounts of MHC class I molecules, a phenomenon that frequently occurs in tumors and virus-infected cells. Each inhibitory receptor is expressed only by a fraction of NK cells. In addition, each NK cell expresses at least one receptor specific for self-MHC alleles. As a consequence, the whole NK cell pool can sense the loss of even single MHC-class I alleles on self cells. NK cells also express surface receptors responsible for the activation during the process of natural cytotoxicity. These recently identified receptors include NKp46 (7 8), NKp30 (9) and NKp44 (10 11), collectively referred to as natural cytotoxicity receptors (NCR) (12). Another receptor which plays a complementary role with NCR in the processo of NK cell activation is NKG2D (13 14), while additional triggering surface molecules expressed by human NK cells, including 2B4 and NKp80, appear to play a role as coreceptors rather than as true receptors (15 16).
KeywordsAcute Myeloid Leukemia Inhibitory Receptor Acute Myeloid Leukemia Cell Tumor Cell Lysis Human Natural Killer Cell
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