Function
HAVCR2 antibody is directed against the cell surface receptor known as TIM-3 (T-cell immunoglobulin and mucin domain-3). This receptor plays a crucial role in modulating both innate and adaptive immune responses, generally exhibiting an inhibitory function. While reports suggest stimulatory functions under certain cellular contexts or with specific ligands, its primary role is considered inhibitory. TIM-3 regulates macrophage activation and exerts a suppressive effect on T-helper type 1 lymphocyte (Th1)-mediated autoimmune and alloimmune responses, promoting immunological tolerance. In CD8+ cells, TIM-3 attenuates TCR-induced signaling by inhibiting NF-κB and NFAT promoter activities, leading to reduced IL-2 secretion. This function may be linked to its association with LCK, potentially hindering phosphorylation of TCR subunits, or LGALS9-dependent recruitment of PTPRC to the immunological synapse. However, TIM-3 has also been demonstrated to activate TCR-induced signaling in T-cells, possibly involving ZAP70, LCP2, LCK, and FYN. When expressed on regulatory T (Treg) cells, TIM-3 can suppress Th17 cell responses. TIM-3 serves as a receptor for LGALS9, and binding to this ligand is believed to result in the suppression of T-cell responses. This suppression may be mediated by the induction of apoptosis in antigen-specific cells, potentially involving HAVCR2 phosphorylation and disruption of its association with BAG6. The interaction between TIM-3 and LGALS9 is also proposed to contribute to the innate immune response to intracellular pathogens. Expressed on Th1 cells, TIM-3 interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages, stimulating antibactericidal activity, including IL-1β secretion, and restricting intracellular bacterial growth. However, the function of TIM-3 as a receptor for LGALS9 has been challenged. TIM-3 has also been reported to enhance CD8+ T-cell responses to acute infections, such as those caused by Listeria monocytogenes. TIM-3 acts as a receptor for phosphatidylserine (PtSer), and this binding is calcium-dependent. This interaction may allow TIM-3 to recognize PtSer on apoptotic cells, leading to their phagocytosis. TIM-3 mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, TIM-3 promotes conjugation but not engulfment of apoptotic cells. On dendritic cells (DCs), TIM-3 positively regulates innate immune responses and, in synergy with Toll-like receptors, promotes the secretion of TNF-α. In tumor-infiltrating DCs, TIM-3 suppresses nucleic acid-mediated innate immune responses by interacting with HMGB1, interfering with nucleic acid sensing and the trafficking of nucleic acids to endosomes. On natural killer (NK) cells, TIM-3 acts as a coreceptor to enhance IFN-γ production in response to LGALS9. However, TIM-3 has also been shown to suppress NK cell-mediated cytotoxicity, negatively regulating NK cell function during LPS-induced endotoxic shock.