Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion.
Authors: Peppa, Dimitra, Gill, Upkar S, Reynolds, Gary, Easom, Nicholas, Pallett, Laura J, Schurich, Anna, Micco, Lorenzo, Nebbia, Gaia, Singh, Harsimra, Adams, David H, Kennedy, Patrick, Maini, Mala K
J Exp Med, 2013;210(1):99-114.
Species: Human
Sample Type: tissue
Application: IHC Paraffin-embedded
Innate immunity in multiple sclerosis white matter lesions: expression of natural cytotoxicity triggering receptor 1 (NCR1).
Authors: Durrenberger PF, Ettorre A, Kamel F
J Neuroinflammation, 2012;9(0):1.
Species: Human
Sample Type: Whole Cells
Application: ICC

NKp46, along with NKp30 and NKp44, are activating receptors that have been collectively termed the natural cytotoxicity receptors (NCR) (1). These receptors lack significant sequence homology to one another. They are expressed almost exclusively by NK cells and play a major role in triggering some of the key lytic activities of NK cells. The CD56^dimCD16⁺ subpopulation that makes up the majority of NK cells in the peripheral blood and spleen expresses NKp46 in both resting and activated states (2). The main NK cell population of the lymph node (CD56^brightCD16^-) expresses low levels of NKp46 in resting cells, but expression is up-regulated by IL-2. NKp46 is a type I transmembrane protein with two extracellular Ig-like domains followed by a short stalk region, a transmembrane domain containing a positively charged amino acid residue, and a short cytoplasmic tail. Through its positive charge in the transmembrane domain, NKp46 associates with the
ITAM-bearing signal adapter proteins, CD3 zeta and Fc epsilon R1 gamma, which are able to form disulfide-linked homodimers and heterodimers (3, 8). Studies with neutralizing antibodies indicate that the three NCRs are primarily responsible for triggering the NK-mediated lysis of many human tumor cell lines. Blocking any of the NCRs individually resulted in partial inhibition of tumor cell lysis, but nearly complete inhibition of lysis was observed if all three receptors were blocked simultaneously (4). NKp46 has also been implicated in recognition of virus-infected cells through its capacity to bind to viral hemagglutinins (5-7). Human NKp46 shares 58% and 59% amino acid sequence identity with the mouse and rat proteins, respectively.

1. Moretta, L. and A. Moretta (2004) EMBO J. 23:255. 
2. Ferlazzo, G. et al. (2004) J. Immunol. 172:1455.
3. Augugliaro, R. et al. (2003) Eur. J. Immunol. 33:1235. 
4. Pende, D. et al. (1999) J. Exp. Med. 190:1505.
5. Arnon, T. et al. (2004) Blood 103:664.
6. Arnon, T. et al. (2001) Eur. J. Immunol. 31:2680.
7. Mandelboim, O. et al. (2001) Nature 409:1055.
8. Moretta, A. et al. (2001) Annu. Rev. Immunol. 19:197.