Phenotypic and functional consequences of different isolation protocols on skin mononuclear phagocytes
Authors: RA Botting, KM Bertram, H Baharlou, KJ Sandgren, J Fletcher, JW Rhodes, H Rana, TM Plasto, XM Wang, JJ Lim, L Barnouti, MP Kohout, T Papadopoul, S Merten, N Olbourne, AL Cunningham, M Haniffa, AN Harman
J. Leukoc. Biol, 2017;0(0):.
Species: Human
Sample Type: Whole Cells
Application: Flow

NKp80, also known as killer cell lectin-like receptor subfamily F member 1 (KLRF1), is an 80 kDa type II transmembrane, homodimeric, activating co‑receptor expressed exclusively on the surface of NK cells. Human NKp80, a member of the C-type lectin family of proteins (1‑3), is 231 aa in length with a 38 amino acid (aa) cytoplasmic region, a 21 aa transmembrane region, and a 172 aa extracellular domain (ECD). The ECD contains the C-type lectin-like domain (aa 114‑230) and four potential sites of N-linked glycosylation. Multiple splicing variants produce four isoforms for NKp80. Isoform 1 is the standard protein. There are no murine orthologs for NKp80 (4). NKp80 functions as an inhibitory receptor based on the presence of two immunoreceptor tyrosine‑based inhibitory motifs (ITIM) in the N-terminal cytoplasmic region and the lack of charged amino acids in the transmembrane region (1). However, later studies show that NKp80 displays an activating function rather than an inhibitory one (2‑3, 5). In in vitro experiments in human NK cells, NKp80 stimulates NK cell cytotoxicity and induces calcium influx after triggering by appropriate antibodies (2, 3). One study reports that NKp80 likely functions as a co‑receptor, cooperating with NKp46 and other activating receptors in NK cell cytotoxicity (2). Activation-induced C-type lectin (AICL) is the ligand for NKp80 (3). It is a myeloid-specific receptor expressed by monocytes, macrophages, and granulocytes (3). Crosslinking of both NKp80 and AICL stimulates secretion of proinflammatory cytokines suggesting that NKp80‑AICL interaction is involved in the activating crosstalk between NK cells and myeloid cells, and thus may influence the initiation and maintenance of immune responses in humans (3).

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2. Vitale, M. et al. (2001) Eur. J. Immunol. 31:233.
3. Welte, S. et al. (2006) Nat. Immunol. 7:1334.
4. Yokoyama, W.M. and B.F. Plougastel (2003) Nat. Rev. Immunol. 3:304.
5. Thomas, M. et al. (2008) Proc. Natl. Acad. Sci. U.S.A. 105:1656.