NKp80 is a C-type lectin-like homodimeric receptor that is mainly expressed by human NK cells and is absent in rodents. Although its natural ligand was not known until now, ligation of NKp80 with a specific antibody stimulates NK-cell cytotoxicity and cytokine release, which is consistent with it being an activating receptor. On the basis of a previous observation that genes for both the mouse NKR-P1 receptor family and their ligands are located in the NK-cell gene complex (NKC), Welte et al. tested two NKC-encoded candidate molecules, AICL and LLT1 (lectin-like transcript 1), for their ability to bind NKp80. Beads coated with recombinant AICL, but not with LLT1, were stained with fluorescent tetrameric complexes of NKp80, implying that AICL might be a ligand for NKp80. Confirming this possibility, AICL tetramers were shown to bind freshly isolated human NK cells, and this binding could be blocked by pre-incubation of the cells with NKp80-specific antibody.
Following identification of AICL as a ligand for NKp80, the authors could then assess the importance of this interaction in a biological setting. AICL was shown to be preferentially expressed by myeloid cells, but not by T cells, B cells or dendritic cells, and its expression could be upregulated by exposure of myeloid cells to Toll-like receptor ligands. So, when human NK cells and myeloid cells (either a cell line or autologous monocytes) were co-cultured, NK-cell-mediated lysis of the myeloid cells occurred. Importantly, lysis could be reduced by the presence of NKp80-specific or AICL-specific antibody in the co-cultures, confirming the involvement of the AICL–NKp80 interaction.
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