TIGIT (WUCAM) is an immunoreceptor that inhibits multiple immune cell responses, including T cell priming by dendritic cells, tumor cell killing by NK cells and cytotoxic T cells, and also enhances the immune suppressive activity of regulatory T cells1. TIGIT is a novel member of the Ig-superfamily distantly related to Nectins and Necls that aligns with the distal Ig-V-type domains of Nectin(1-4), poliovirus receptor (PVR; CD155), DNAM-1 (CD226), and TACTILE (CD96)2. TIGIT is preferentially expressed on human B helper follicular T cells and binds with high affinity to PVR under both static and flow conditions. Additionally, TIGIT, DNAM-1, and TACTILE are expressed together on T cells and NK cells and share PVR as a ligand1. TIGIT is not detectable on the surface of resting peripheral blood mononuclear cells from healthy donors unless activated2.
4E1.2 was generated by immunizing BALB/c mice with TIGITFLAG-Baf3 cells2. Baf3 cells transfected with TIGIT cDNA are specifically stained by 4E1.2. Blocking with 4E1.2 significantly reduces PVR-hFc binding to TIGIT/Baf3 and to ICOShigh CD4+ T cells. TIGIT-PVR interactions are important for regulating T cell function and contribute to T cell-dependent B cell responses.
TIGIT is an attractive target for cancer therapy due to its role as an immune checkpoint1. Immunotherapy targeting TIGIT and the PD-1/PD-L1 pathway is capable of tumor suppression. Other combinations, such as TIGIT with TIM-3, CD112R, or TACTILE, have also shown promise in blocking studies.