Cayman TIM-3 Rabbit Monoclonal Antibody (Clone RM448)

TIM-3 is a member of the T-cell immunoglobulin and mucin-domain containing (TIM) protein family of immunoregulatory proteins and is encoded by the HAVCR2 gene in humans.¹ It is a transmembrane protein composed of an N-terminal immunoglobulin variable (IgV) domain, as well as mucin stalk, transmembrane, and C-terminal cytoplasmic tail domains. The IgV domain contains cysteine residues that form non-canonical intramolecular disulfide bonds resulting in a cleft and channel not found in non-TIM immunoglobulin domains that is important for non-canonical ligand binding.² TIM-3 is expressed primarily on T cells but is also expressed on other immune cells such as natural killer and dendritic cells.³ The TIM-3 ligand galectin 9 (Item No. 32012), located on immune or tumor cells, binds to glycosylated sites of the IgV and mucin stalk domains and induces TIM-3 oligomerization to activate downstream signaling that impairs immune synapse formation and leads to T cell anergy or apoptosis.¹ The TIM-3 IgV cleft domain binds non-canonical ligands, such as phosphatidylserine on apoptotic cells or CEACAM1 on antigen-presenting or tumor cells.^2,1,3 TIM-3 is an inhibitory co-receptor that helps maintain immune tolerance but, when expressed on certain cells during chronic infection or cancer, can lead to immune exacerbation.³ Inhibition of the TIM-3 pathway by Tim-3 fusion or extracellular domain-only proteins prevents the induction of immune tolerance in a mouse islet allograft model or increases weight loss and tissue injury in a mouse model of TNBS-induced colitis, respectively.^4,5 Expression of TIM-3 is decreased in patients with autoimmune diseases, including ulcerative colitis.^1,6 TIM-3 is expressed on tumor-infiltrating T cells and expressed on a higher proportion of regulatory T cells from cancer patients.¹ Its overexpression on T cells increases tumor progression in an EL4 mouse model of lymphoma, while TIM-3 inhibition decreases tumor growth in a mouse model of head and neck cancer. SNPs in HAVCR2 are associated with allergic diseases, immunity, and cancer. Caymans TIM-3 Rabbit Monoclonal Antibody (Clone RM448) can be used for immunohistochemistry (IHC) and Western blot (WB) applications.

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