TIM-3 Fc

T‐cell immunoglobulin mucin receptor 3 (TIM‐3), or HAVcr‐2, is a type I transmembrane receptor of the immunoglobulin superfamily involved in modulating innate and adaptive immune responses. TIM‐3 is expressed in T cells, including Th1, Th17, CD4+, CD8+, NK, and Tregs, as well as myeloid cells, including macrophages, monocytes and dendritic cells. TIM‐3 displays predominantly inhibitory functions, however recent studies have demonstrated stimulatory effects in select cell types. TIM‐3 is a relevant marker of T cell exhaustion and its expression directly correlates with chronic viral disease progression and tumor progression in a wide range of cancers. TIM‐3 expression is downregulated in autoimmune disorders such as MS, RA and psoriasis. Interaction of TIM‐3 and its ligands suppresses T cell responses and induces immune tolerance. Four ligands, Gal‐9, PtdSer, HMGB1, and Ceacam‐1, have been identified, each inducing distinct responses upon engagement. Gal‐9 ligation prompts an influx of Ca+ to the intracellular region, inducing apoptosis in T cells and NK cells. Binding PtdSer, a molecule found on the surface of apoptotic cells, promotes cross presentation of antigens and regulation of innate immune response in DCs and macrophages. HMGB1 triggers innate immune responses following interaction with nucleic acids released from dying cells; however, TIM‐3 actively competes with this interaction by attenuating immune response upon binding to HMGB1. Ceacam‐1 is co‐expressed on the cell surface with TIM‐3, where it forms heterodimers that lead to negative regulation of T cell responses. The naturally occurring human TIM‐3 monomer consists of a 181‐amino‐acid extracellular domain, a 21‐amino‐acid transmembrane domain, and a 78‐amino‐acid cytoplasmic domain. CHO cell‐derived Recombinant Human TIM‐3 Fc is a glycosylated, disulfide‐linked homodimer of 412‐amino‐acid‐residues whose monomer consists of a 179‐amino acid portion of the extracellular domain fused to the 231‐amino‐acid length Fc portion of human IgG by two glycine residues. The calculated molecular weight of monomeric CHO cell‐derived Recombinant Human TIM‐3 Fc is 45.9 kDa; however, due to glycosylation, it migrates at an apparent molecular weight of approximately 180‐200 kDa by SDS‐PAGE analysis under non‐reducing conditions.