4-­1BB, also known as CD137, ILA and TNFRSF9, is a single-pass type I transmembrane glycoprotein of the TNF receptor superfamily (TNFRSF). 4­1BB is expressed as a disulfide­linked homodimer on activated T cells.  4-1BB is absent from naive T cells, but its expression is induced by lymphocyte activation. 4-1BB is the receptor for 4-1BB ligand/TNFSF9, which is expressed on antigen-presenting cells such as macrophages and activated B cells. 4-1BB mediated signaling pathway contributes to the proliferation, survival, and development of T cells. 4-1BB can also promote proliferation in peripheral monocytes, enhance T cell apoptosis triggered by TCR-CD3 activation, and regulate CD28 co-stimulation to promote Th1 cell responses.  4­1BB deficient mice show augmented T cell activation.  4-1BB and its ligand are also expressed in different human tumor tissues. 4­-1BB activation by crosslinking with its ligand or agonistic antibody enhances cytotoxic T cell and NK cell mediated anti­tumor immunity. 4­-1BB can interact with OX40 on activated T cells, forming a complex that responds to either ligand and inhibits Treg and CD8+ T cell proliferation.  4-1BB may also be involved in the development of inflammation in high fat diet­induced metabolic syndrome. The soluble form of 4­-1BB circulates at elevated levels in the serum of rheumatoid arthritis. 

4-­1BB, also known as CD137, ILA and TNFRSF9, is a single-pass type I transmembrane glycoprotein of the TNF receptor superfamily (TNFRSF). 4­1BB is expressed as a disulfide­linked homodimer on activated T cells.  4-1BB is absent from naive T cells, but its expression is induced by lymphocyte activation. 4-1BB is the receptor for 4-1BB ligand/TNFSF9, which is expressed on antigen-presenting cells such as macrophages and activated B cells. 4-1BB mediated signaling pathway contributes to the proliferation, survival, and development of T cells. 4-1BB can also promote proliferation in peripheral monocytes, enhance T cell apoptosis triggered by TCR-CD3 activation, and regulate CD28 co-stimulation to promote Th1 cell responses.  4­1BB deficient mice show augmented T cell activation.  4-1BB and its ligand are also expressed in different human tumor tissues. 4­-1BB activation by crosslinking with its ligand or agonistic antibody enhances cytotoxic T cell and NK cell mediated anti­tumor immunity. 4­-1BB can interact with OX40 on activated T cells, forming a complex that responds to either ligand and inhibits Treg and CD8+ T cell proliferation.  4-1BB may also be involved in the development of inflammation in high fat diet­induced metabolic syndrome. The soluble form of 4­-1BB circulates at elevated levels in the serum of rheumatoid arthritis. 

 

Product Details

 

Gene Symbol: 4-1BB;CD137; ILA; TNFRSF9; CDw137; MGC2172

 

NCBI Gene ID: 3604

 

Uniprot Entry: Q07011

 

Construct Details: The recombinant human 4-1BB-Fc fusion is expressed as a 390 amino acid protein consisting of Leu24 - Gln186 region of 4-1BB (UniProt accession #Q07011)  and a C-terminal Fc from human IgG1, which exists as a dimer/tetramer under non-reducing conditions (see the gel image above).  

 

Source: Human cells stably expressing human 4-1BB/CD137 and growing in chemical-defined media with no animal components or antibiotics

 

Deduced Amino Acid Sequence:

LQDPCSNCPAGTFCDNNRNQICSPCPPNSFSSAGGQRTCDICRQCKGVFRTRKECSSTSNA

ECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKDCCFGTFNDQKRGICRPWTNCSLDGKS

VLVNGTKERDVVCGPSPADLSPGASSVTPPAPAREPGHSPQTGTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ

VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

 

M.W.: Calculated molecular mass (kDa): 42.8; Estimated by SDS-PAGE under reducing condition (kDa): 55-60

 

Calculated PI: 7.72

 

Calculated extinction coefficients (M-1 cm-1, at 280nm):  42535

 

Purity: >90% judged by SDS-PAGE under reducing condition (see the gel image above, labeled as "DTT: +")

 

Formulation: Supplied at 0.5 mg/ml in sterile PBSpH7.4 (carrier & preservative free). The purified recombinant protein was labeled with Biotin (3-5 Biotin per molecule) using the standard procedure.

 

Endotoxin Level: <0.1 EU per 1 μg of purified recombinant protein determined by the LAL method

 

Biological Activity: Binds to its ligand human 4-1BBL and anti-4-1BB monoclonal antibodies (SKU#MAB1829) with high affinity by ELISA (see Technical Data). Blocks 4-1BBL/4-1BB-­induced signaling activity.

 

 

  

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.

 

Technical Data

 

Recombinant 4-1BB/CD137-Fc protein (SKU#FCL0100) was immobilized at 100 ng/well on a 96-well NuncMaxisorp plate for ELISA with serially diluted biotinylated anti-4-1BB/CD137 monoclonal antibody, human IgG1 (SKU#MAB1829B). Biotinylated anti-CD28 (SKU#MAB1827B) human IgG1 was used as a control to demonstrate the specificity of 4-1BB/CD137 binding under the experimental conditions.  The binding curve was fit and apparent K_D was calculated for anti-4-1BB: 4-BB binding to be 51 ± 5pM.  

 

 

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

 

Storage

 

The product is shipped at 4°C. Upon receipt, centrifuge the product briefly before opening the vial. It is recommended to store small aliquots at the temperature below –20°C for long-term storage and the product is stable for 3 months. The undiluted protein can be stored at 4°C for no more than 2 weeks.

 

 

Use a manual defrost freezer and avoid repeated freeze-thaw cycles.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

 

References

 

1. J. Immunol. 168:4897 (2002).

2. Nat. Immunol. 9:917 (2008).

3. Trends Pharmacol. Sci. 29(8): 383 (2008).

4. Immunol. Rev. 229:192 (2009).

5. Diabetes 60:3159 (2011).

 

 

Documentation

 

Product datasheet (pdf) can be downloaded here: FCL0100B-PDS.pdf

 

 

 

Additional supporting documents, including COA and MSDS are available upon request.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.