Killer cell lectin-like receptor subfamily F member 1 (KLRF1 also referred as NKp80 or CLEC5C) is a homodimeric C-type lectin receptor (CTLR) expressed virtually on all human NK cells, and a minor subsets of effector memory CD8 alpha/beta T cells and gamma/delta T cells (Vitale et al. 2001). NKp80 binds to the genetically linked receptor C-type lectin domain family 2 member B (CLEC2B also referred as AICL) (Welte et al. 2006). CLEC2B is expressed as a myeloid-specific activating receptor that is upregulated by Toll-like receptor stimulation (Hamann et al. 1997). NKp80-CLEC2B interaction triggers NK cell-mediated cytolysis of malignant myeloid cells. Crosslinking of both NKp80 and CLEC2B was shown to promote an activating cross-talk between NK cells and monocytes in the presence of inflammatory cytokines (Welte et al. 2006, Klimosch et al. 2013).