Supplementary Data 1 from Human Breast Tumor Cells Induce Self-Tolerance Mechanisms to Avoid NKG2D-Mediated and DNAM-Mediated NK Cell Recognition
PDF file - 320K, Supplemental Data 1: Ligands and receptors respectively expressed by tumor and NK-cells. Natural killer (NK) cells are components of the innate immune system that play a central role against tumor cells. They have an innate ability to distinguish normal from "modified" cells, such as cancer cells, through a broad range of activating and inhibitory receptors. These receptors act like little sensors of the malignant self (Moretta et al, 2006); the integration of these opposite signals determines whether an NK-cell will eliminate a potential target or not. NK-cell activating receptors are the natural cytotoxicity receptors (NKp30, NKp46 and NKp44) and NKG2D. They recognize various ligands expressed by transformed cells and/or stressed or activated cells. To date, NKp30 has two described ligands, B7H6 and BAT3. NKG2D can bind MICA, MICB and the members of the ULBP family. The ligand(s) of NKp46 or NKp44 are unknown. The main NK-cell inhibitory receptors are the killer immunoglobulin receptors (KIRs) and NKG2A (Moretta et al., 1995 & 2001), which recognize members of the HLA-I family expressed by normal cells, respectively HLA-A, -B or -C for the KIRs and HLA-E for NKG2A. The signal is fine-tuned by co-activators such as DNAM-1, CD2, NKp80, 2B4, NTBA and co-inhibitors such as the CD85 family, B7-H3 or LAIR. Among co-activator receptors, DNAM-1 binds the heterodimer PVR/Nectin2 receptors, CD2 binds CD58, NTBA binds another NTBA molecule, and 2B4 binds CD48. The co-inhibitory receptors from the CD85 family bind HLA-I molecules, while ligands of the LAIR family and B7H3 are still unknown.