TREM2-CLuc-IRES-TYROBP-NLuc split-Renilla luciferase reporter system. The TREM2-CLuc-IRES-TYROBP-NLuc vector contains CMV immediate early (IE) promoter, the C terminus of the Renilla luciferase gene fused to the cytoplasmic region of TREM2 (TREM2-CLuc), IRES, and the N-terminal region of the Renilla luciferase gene fused to the N-terminal region of TYROBP (TYROBP-NLuc) (A). The unique restriction sites for cloning are depicted. Ampr, ampicillin resistance gene; Neor, neomycin resistance gene. In a resting state, wild-type TREM2 and TYROBP show limited coupling. Upon stimulation with agonistic ligand (such as dimerizing anti-TREM2 antibody), TREM2 interacts with TYROBP, which reconstitutes luciferase activity by coupling of the C- and N-terminal regions of the split-Renilla luciferase gene (B).