TIM-3 Products

Description

T cell immunoglobulin and mucin-domain containing 3 (TIM-3) is a type I transmembrane protein that functions in suppressing immune cell responses and is considered a checkpoint receptor (1,2). TIM-3 is an inhibitory receptor that was first identified as a cell marker for interferon-gamma (IFN-gamma)-producing CD4+ T helper (Th1) and CD8+ T cytotoxic (Tc1) cells (1,2). TIM-3 is also expressed on other immune cell types: regulatory T cells (Treg), natural killer (NK) cells, macrophages, and dendritic cells (DCs), as well as leukemia stem cells (LSCs) (1-3). Human TIM-3 protein is 301 amino acids (aa) in length with a theoretical molecular weight (MW) of 33.4 kDa and shares ~63% aa sequence identity with mouse TIM-3 (2,4). The TIM-3 protein has an extracellular IgV domain, a mucin and stalk domain with O- and N-glycosylation sites, a transmembrane domain, and an intracellular tail with conserved tyrosine residues (2,3). Ligands for TIM-3 include soluble galectin-9, high-mobility group protein B1 (HMGB1), phosphatidylserine (PtdSer), and carcinoembyronic antigen-related cell adhesion molecule-1 (CEACAM-1) (1-3,5). Each of these ligands interact with different regions of the TIM-3 IgV domain. In the absence of ligand binding, the unphosphorylated intracellular tyrosine residues of TIM-3 are associated with HLA-B associated transcript 3 (Bat3), which recruits Lck and this Bat3-Lck complex preserves T cell signaling (1-3,5). When TIM-3 is engaged, an intracellular signaling cascade is initiated to inhibit immune cell activation. (1-3,5). Specifically, the tyrosine residues of TIM-3 are phosphorylated, Bat3 is released, and this results in suppression of immune responses (1-3, 5). Persistent, sustained TIM-3 signaling eventually results in T cell exhaustion (1-3,5).

Dysregulation of TIM-3 expression is associated with autoimmune diseases as shown by studies where inhibition of TIM-3 using blocking antibodies worsened disease progression in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis (MS) (2,3,5). Conversely, high levels of TIM-3 have been shown during viral infection as well as in many cancer types where its increased expression may be an indicator of poor prognosis (2,3,5). TIM-3 has emerged as a potential cancer immunotherapy target as preclinical studies blocking TIM-3 results in increased anti-tumor immunity and prevents tumor growth (3,5). Studies have suggested combination therapy of TIM-3 blockade with blockade of other checkpoint inhibitors such as programmed death 1 (PD-1) or lymphocyte activation gene 3 (LAG-3) is more effective than TIM-3 blockade alone (3,5).

References

1. Acharya N, Sabatos-Peyton C, Anderson AC. Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 2020; 8(1):e000911. https://doi.org/10.1136/jitc-2020-000911

2. Das M, Zhu C, Kuchroo VK. Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 2017; 276(1):97-111. https://doi.org/10.1111/imr.12520

3. Joller N, Kuchroo VK. Tim-3, Lag-3, and TIGIT. Curr Top Microbiol Immunol. 2017; 410:127-156. https://doi.org/10.1007/82_2017_62

4. Uniprot (Q8TDQ0)

5. Wolf Y, Anderson AC, Kuchroo VK. TIM3 comes of age as an inhibitory receptor. Nat Rev Immunol. 2020; 20(3):173-185. https://doi.org/10.1038/s41577-019-0224-6

Bioinformatics

Entrez	171285 Mouse 84868 Human
Uniprot	AAH20843 Human NM_032782 Human NP_116171 Human NP_116171.3 Human Q8TDQ0 Human Q8VIM0 Mouse
Product By Gene ID	84868
Alternate Names	CD366 FLJ14428 HAVcr-2 hepatitis A virus cellular receptor 2 kidney injury molecule-3 T cell immunoglobulin mucin 3 T cell immunoglobulin mucin-3 T-cell immunoglobulin and mucin domain-containing protein 3 TIM 3 TIM3 T-cell membrane protein 3 Tim-3 TIMD-3 TIMD3KIM-3

Research Areas for TIM-3

Find related products by research area and learn more about each of the different research areas below.

Immunology
Innate Immunity

Related TIM-3 Blog Posts

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TIM-3, a critical immune checkpoint in HIV research CD4+ T-helper cells (Th) are the white blood lymphocytes expressing surface glycoprotein antigen CD4. These T-helper cells play an important role in the adaptive immune system by releasing T cell cytokines that help other immune cells to suppress o...    Read more.

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