Anti-TIM-3/HAVCR2

T cell immunoglobulin and mucin domain-3 (TIM3), also called hepatitis A virus cellular receptor 2 (HAVCR2), isa transmembrane glycoprotein of the TIM family of immune regulating molecules and plays an important rolein the Th1-mediated immune response. TIM3 is expressed on the Th1 cells, CD8 T-cells, monocytes, anddendritic cells, but not on Th2 cells. TIM3 expressed by monocytes and dendritic cells facilitates phagocytosisof apoptotic cells and up-regulates cross-presentation of apoptotic cell-associated antigens through interactionwith phosphatidylserine. Engagement of TIM3 by its ligand galectin-9 induces a range of immunosuppressivefunctions which enhance immune tolerance and inhibit anti-tumor immunity. Stimulation of TIM3 with anagonistic antibody promotes inflammation through the activation of innate immune cells. TIM3 is alsoregarded as a potential target molecule for immunotherapy. TIM3 and programmed cell death 1 (PD-1) as twoimportant coinhibitory regulators of T cell responses, have been implicated with the T-cell dysfunction orexhaustion associated with chronic HBV infection including HBV-related HCC. Protein function: Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:18006747). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556006, PubMed:18006747). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits. In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell responses. Receptor for LGALS9. Binding to LGALS9 is believed to result in suppression of T-cell responses, the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6 (PubMed:22863785). Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis- infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (PubMed:20937702). However, the function as receptor for LGALS9 has been challenged. Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (PubMed:24567532). Receptor for phosphatidylserine (PtSer), PtSer- binding is calcium-dependent (PubMed:20083673). May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells (PubMed:20083673). Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha (PubMed:18006747). In tumor- imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid- sensing and trafficking of nucleid acids to endosomes (PubMed:22842346). Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity. Negatively regulates NK cell function in LPS-induced endotoxic shock (PubMed:25337993). [The UniProt Consortium]