Natural Killer (NK) cells are innate functions immune cells, derived from the lymphoid lineage, which contribute to the destruction of cancer cells and virus infected cells. After forming a so called immunological synapse NK cells release granzymes and perforin from stored cytotoxic granules, which trigger apoptotic cell death in the target cells. We have assays available to study the capacity of NK to destroy antibody-opsonized cancer cells, by a process known as antibody-dependent cellular cytotoxicity (ADCC), and to measure their degranulation capacity. There is a considerable level of genetic variation that occurs among the various NK surface receptors, including both Fcg receptor and killer immunoglobulin-like receptors (KIR), that is relevant for the killing process. We have various multiplex ligation dependent probe amplification (MLPA) assays available to determine the individual genotypes of essentially all of these receptors.
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Like other immune cells such as phagocytes also NK cells express certain Fc receptors for IgG antibodies, in particular FcgRIIIa. Opsonization of target cells, such as cancer cells or virus infected cells, by endogenous or therapeutic antibodies, triggers ADCC by NK cells towards those target cells. There exists considerable genetic variation among human FcgR, including single nucleotide polymorphisms (colored residues) and gene copy number variation (CNV) and this forms an important determinant with respect to killing capacity.
Kuijpers TW, Baars PA, Dantin C, van den Burg M, van Lier RA, Roosnek E. Human NK cells can control CMV infection in the absence of T cells. Blood 2008; 112(3):914-5.
Breunis WB, van Mirre E, Geissler J, Laddach N, Wolbink G, van der Schoot E, de Haas M, de Boer M, Roos D, Kuijpers TW. Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B. Hum Mutat 2009; 30(5):E640-50.
Van der Heijden J, Breunis WB, Geissler J, de Boer M, van den Berg TK, Kuijpers TW. Phenotypic variation in IgG receptors by nonclassical FCGR2C alleles. J Immunol 2012; 188(3):1318-24.
Vendelbosch S, de Boer M, Gouw RA, Ho CK, Geissler J, Swelsen WT, Moorhouse MJ, Lardy NM, Roos D, van den Berg TK, Kuijpers TW. Extensive variation in gene copy number at the killer immunoglobulin-like receptor locus in humans. PLoS One 2013; 8(6):e67619.
Vendelbosch S, de Boer M, van Leeuwen K, Pourfarzad F, Geissler J, van den Berg TK, Kuijpers TW. Novel insights in the genomic organization and hotspots of recombination in the human KIR locus through analysis of intergenic regions. Genes Immun 2015; 16(2):103-11.
Nagelkerke SQ, Kuijpers TW. Immunomodulation by IVIg and the Role of Fc-Gamma Receptors: Classic Mechanisms of Action after all? Front Immunol 2015; 5:674.
Vendelbosch S, de Boer M, van der Heijde D, van den Berg TK, van Gaalen FA, Kuijpers TW. KIR3DL1 and KIR3DL2 gene copy number variation in axial spondyloarthritis. Tissue Antigens 2015; 85(6):497-8.
Vendelbosch S, Heslinga SC, John M, van Leeuwen K, Geissler J, de Boer M, Tanck M, van den Berg TK, Crusius J, van der Horst-Bruinsma IE, Kuijpers TW. Study on the protective effect of the KIR3DL1 gene in Ankylosing Spondylitis. Arthritis Rheumatol 2015 Aug 3.