Human TIM-3 Antibody

TIM-3 (T cell immunoglobulin and mucin domain-3) 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 (1-3). There are three TIM genes in human and eight in mouse. Mature human TIM-3 consists of a 181 amino acid (aa) extracellular domain (ECD), a 21 aa transmembrane segment, and a 78 aa cytoplasmic tail (4). An alternately spliced isoform is truncated following a short substitution after the Ig-like domain. Within the ECD, human TIM-3 shares 58% aa sequence identity with mouse and rat TIM-3. TIM-3 is expressed on the surface of effector T cells (CD4⁺ Th1 and CD8⁺ Tc1) but not on helper T cells (CD4⁺ Th2 and CD8⁺ Tc2) (4, 5). In chronic inflammation, autoimmune disorders, and some cancers, TIM-3 is upregulated on several other hematopoietic cell types. It also occurs on hippocampal neurons (7-10). The Ig domain of TIM-3 interacts with a ligand on resting but not activated Th1 and Th2 cells (5, 11). The glycosylated Ig domain of TIM-3 binds cell-associated galectin-9. This induces TIM-3 Tyr phosphorylation and pro-apoptotic signaling (8, 12). TIM-3 functions as a negative regulator of Th1 cell activity. Its blockade results in increased IFN-gamma production, Th1 cell proliferation and cytotoxicity (5, 10, 11, 13), regulatory T cell development (5), and increases in macrophage and neutrophil infiltration into sites of inflammation (14). Soluble mouse TIM-3 constructs which lack the cytoplasmic domain have been shown to inhibit anti-tumor effector T cell responses and to enhance autoimmune reactions (5, 15).