AITRL/TNFSF18 Trimer Protein, Human (HEK293, His-Flag)

AITRL, a type II transmembrane protein, is a ligand for glucocorticoid-induced TNFR-related protein (GITR). When AITRL binds to GITR, GITR can produce costimulatory signals that regulate T-cell proliferation and effector functions. GITR/AITRL interaction plays a role in the pathogenesis of tumor, inflammation, as well as autoimmune diseases^[1]. Besides, AITRL plays a role in endothelial cells (EC)-activation and increases STAT-1 phosphorylation and the expression of adhesion molecules (VCAM-1, ICAM-1)^[2]. AITRL/TNFSF18 Trimer Protein, Human (HEK293, His-Flag) is a recombinant human AITRL (Q72-S199) trimer with N-terminal His and Flag tag, which is expressed in HEK293.

GITRL (AITRL), a type II transmembrane protein, is a ligand for glucocorticoid-induced TNFR-related protein (GITR). GITR, a member of the TNFR superfamily, is expressed in T cells, natural killer cells and some myeloid cells. And GITRL is mainly expressed on antigen presenting cells (B cells, dendritic cells), macrophages and endothelial cells (ECs)^[1].
When GITRL binds to GITR, GITR can produce costimulatory signals that regulate T-cell proliferation and effector functions. The interaction stimulates proliferation and cytokine production of both CD4⁺ Teff and Treg cells, and drives antitumor activity of CD8⁺ T cells^[3]. Besides, GITRL plays a role in EC-activation and promotes adhesion in both mice and humans, which increases STAT-1 phosphorylation and the augmented expression of adhesion molecules such as VCAM-1 and ICAM-1^[2].
Human GITRL shares < 55% common aa identity with mouse. Human GITRL consists of cytoplasmic domain (M1-W27), helical domain (L28-F48), and extracellular domain (L49-S177). Human GITRL is a trimer, but can also be a monomer or assemble in other multimeric structures^[4].
GITR/GITRL interaction plays a role in the pathogenesis of tumor, inflammation, as well as autoimmune diseases^[1].

AITRL (human, 48 h) reduces the suppressive capacity of MDSCs on CD4⁺ T cells (MDSCs induced from healthy donors)^[5].

Immobilized Human GITR Ligand Trimer, His Tag at 2 μg/mL (100 μl/well) on the plate. Dose response curve for Human GITR, hFc Tag with the EC₅₀ of 0.44 μg/mL determined by ELISA.

Human

HEK293

N-His;N-Flag

Q9UNG2 (Q50-S177)

8995  [NCBI]

QLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

50-70 kDa

Greater than 95% as determined by Tris-Bis PAGE.

Lyophilized powder.

Lyophilized a 0.22 μm filtered solution of PBS, pH 7.4. Normally 5% trehalose is added as protectant before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Tian J, et al. The Role of GITR/GITRL Interaction in Autoimmune Diseases. Front Immunol. 2020 Oct 9;11:588682.  [Content Brief]

  [2]. Lacal PM, et al. Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion. J Pharmacol Exp Ther. 2013 Oct;347(1):164-72.  [Content Brief]

  [3]. Wang F, et al. Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions. Nat Commun. 2021 Mar 2;12(1):1378.  [Content Brief]

  [4]. Placke T, et al. Glucocorticoid-induced TNFR-related (GITR) protein and its ligand in antitumor immunity: functional role and therapeutic modulation. Clin Dev Immunol. 2010;2010:239083.  [Content Brief]

  [5]. Tian J, et al. Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjögren Syndrome. J Immunol. 2019 Mar 15;202(6):1693-1703.  [Content Brief]