| TIM3 (T cell immunoglobulin and mucin domain-3), also known as HAVCR2, is a 60kD member of the TIM family of immune regulating molecules. TIMs are type I transmembrane glycoproteins with one Ig-like-V-type domain and a Ser/Thrrich mucin stalk region (1, 2). Mature cynomolgus TIM-3 consists of a 182 amino acid (aa) extracellular domain (ECD), a 21aa transmembrane segment, and a 78aa cytoplasmic tail. Within the ECD, cynomolgus (or crab-eating macaque) monkey TIM-3 shares 81%, 57%, and 56% aa sequence identity with human, mouse, and rat TIM-3, respectively. TIM-3 is up-regulated on several populations of activated myeloid cells (macrophage, monocyte, dendritic cell, microglia, mast cell) and T cells (Th1, CD8+, NK, Treg) (3-10). Its binding to Galectin-9 induces a range of immunosuppressive functions which enhance immune tolerance and inhibit anti-tumor immunity (11). TIM-3 ligation attenuates CD8+ and Th1 cell responses (11-13) and promotes the activity of Treg and myeloid derived suppressor cells (8, 11, 13, 14). In addition, dendritic cell-expressed TIM-3 dampens inflammation by enabling the phagocytosis of apoptotic cells and the cross-presentation of apoptotic cell antigens (3). It also binds the alarmin HMGB1, thereby preventing the activation of TLRs in response to released tumor cell DNA (6). Soluble TIM3 is also reported to inhibit the response of T cells to both Ag-induced and concurrent CD3/CD28 stimulation (15). By contrast, TIM-3 interactions with Galectin-9 can trigger immune stimulatory effects, such as the coactivation of NK cell cytotoxicity (10). Source: HEK293 derived recombinant protein corresponding to Cynomolgus Macaque TIM-3, Fc Chimera Sequence: Cynomolgus macaque TIM-3, Ser22-Arg201 (Accession EHH54703) - IEGRMD - Human IgG1, Pro100-Lys330 (Disulfide-linked homodimer) Molecular Weight (predicted): 46.3kD (monomer) Molecular Weight (SDS-PAGE, reducing) ~60-75kD Activity: Measured by its ability to inhibit anti-CD3 antibody induced IL-2 secretion in human T lymphocytes. The ED50 for this effect is typically 0.5-3ug/ml. Endotoxin: <0.10EU/1ug (LAL method). Storage and Stability: Lyophilized and reconstituted products are stable for 6 months after receipt at -20C. Reconstitute with sterile PBS. Aliquot to avoid repeated freezing and thawing. Store at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer. |
