Anti-NCR1 monoclonal antibody, clone AKS1 [R-PE]

The chromosomal region 19q13.4 harbors the human leukocyte receptor cluster (LRC) which has been demonstrated to contain over 25 genes encoding leukocyte-expressed receptors of the immunoglobulin superfamily. Among these are the killer cell inhibitory receptors (KIR), immunoglobulin like transcripts (ILT), leukocyte associated inhibitory receptors (LAIR), the Fc receptor for IgA (FCAR) as well as the gene for NCR1. ILTs are a family of homologous receptors with two or four immunoglobulin domains. We have determined the genomic organization of ILT11, a novel member of this family that comprises only two immunoglobulin domains. These are most homologous to the first and second immunoglobulin domain of four domain ILTs. ILT11 has a short cytoplasmic tail and a charged amino acid in its transmembrane region, which is characteristic of an activatory receptor. Additionally, the translation starts at a different codon, if compared to other family members.

NK cells employ a variety of activating receptors to kill virally infected and tumor cells. Prominent among these receptors are the natural cytotoxicity receptors (NCRs) (NKp30, NKp44, and NKp46), of which only NKp46 has a mouse ortholog (NCR1). The tumor ligand(s) of NKp46/NCR1 is still unknown, but it was shown that the human NKp46 and the mouse NCR1 are involved in tumor eradication both in vitro and in vivo. Whether any of the NK activating receptors is involved in the prevention of tumor metastasis is unknown. To address this question, we studied the activity of the NK cell receptor NKp46/NCR1 in two spontaneous metastasis models, the B16F10.9 melanoma (B16) and the Lewis lung carcinoma (D122) in the NCR1 knockout mouse that was generated by our group, in various in vitro and in vivo assays. We demonstrated that all B16 and D122 tumors, including those generated in vivo, express an unknown ligand(s) for NKp46/NCR1. We have characterized the properties of the NKp46/NCR1 ligand(s) and demonstrated that NKp46/NCR1 is directly involved in the killing of B16 and D122 cells. Importantly, we showed in vivo that NKp46/NCR1 plays an important role in controlling B16 and D122 metastasis. Thus, to our knowledge, in this study we provide the first evidence for the direct involvement of a specific NK killer receptor in preventing tumor metastasis. The Journal of Immunology, 2012, 188: 2509-2515.