Recombinant Cynomolgus Monkey TIM-3 Fc Chimera Protein, CF

TIM‑3 (T cell immunoglobulin and mucin domain‑3), also known as HAVCR2, is a 60 kDa 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/Thr‑rich mucin stalk region (1, 2). Mature cynomolgus TIM‑3 consists of a 182 amino acid (aa) extracellular domain (ECD), a 21 aa transmembrane segment, and a 78 aa 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 TIM‑3 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).