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. Cayman's TIM-3 Rabbit Monoclonal Antibody (Clone RM448) can be used for immunohistochemistry (IHC) and Western blot (WB) applications.

WARNING This product is not for human or veterinary use.

1. Wolf, Y., Anderson, A.C., and Kuchroo, V.K. TIM3 comes of age as an inhibitory receptor. Nat. Rev. Immunol. 20(3), 173-185 (2020).

2. Cao, E., Zang, X., Ramagopal, U.A., et al. T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface. Immunity 26(3), 311-321 (2007).

3. DeKruyff, R.H., Bu, X., Ballesteros, A., et al. T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells. J. Immunol. 184(4), 1918-1930 (2010).

4. Sabatos, C.A., Cakravarti, S., Cha, E., et al. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat. Immunol. 4(11), 1093-1101 (2003).

5. Li, X., Chen, G., Li, Y., et al. Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease. Clin. Immunol. 134(2), 169-177 (2009).

6. Shi, F., Guo, X., Jiang, X., et al. Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T cell function in ulcerative colitis. Clin. Immunol. 145(3), 230-240 (2012).