Cytotoxic T-lymphocyte antigen 4 (CTLA4), aslo known as CD152, is a single pass type I transmembrane glycoprotein of the Ig superfamily. It is composed of an IgV-type extracellular domain, a transmembrane domain, and a cytoplasmic tail.  CTLA4 is the founding member of the CD28/CTLA-4 family. Members of the CD28/CTLA-4 family either promote T cell activation (CD28 and ICOS) or inhibit T cell activation (CTLA4 and PD­1).  Both CTLA-4 and CD28 bind to the same B7 family ligands, CD80/B7-1 and CD86/B7-2.  CTLA-4 binds to B7-1 and B7-2 with a 20-100 fold higher affinity than CD28.  The CTLA4 gene is widely expressed with highest levels in lymphoid tissues.  It is detected in activated T-cells where expression levels are 30- to 50-fold less than CD28 on the cell surface following activation. Mutations in CTLA4 gene is associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.  Alternate transcriptional splice variants, encoding different isoforms of CTLA4, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. The engineered CTLA4-Fc fusion proteins inhibit T-cell-dependent immune responses and are used as immunosuppressive agents by acting as a competitive inhibitor of CD28. Blockade of CTLA4 inhibitory activity with monoclonal antibodies enhances antitumor immunity and has been proven to be an effective approach for cancer immunotherapy. 

Cytotoxic T-lymphocyte antigen 4 (CTLA4), aslo known as CD152, is a single pass type I transmembrane glycoprotein of the Ig superfamily. It is composed of an IgV-type extracellular domain, a transmembrane domain, and a cytoplasmic tail.  CTLA4 is the founding member of the CD28/CTLA-4 family. Members of the CD28/CTLA-4 family either promote T cell activation (CD28 and ICOS) or inhibit T cell activation (CTLA4 and PD­1).  Both CTLA-4 and CD28 bind to the same B7 family ligands, CD80/B7-1 and CD86/B7-2.  CTLA-4 binds to B7-1 and B7-2 with a 20-100 fold higher affinity than CD28.  The CTLA4 gene is widely expressed with highest levels in lymphoid tissues.  It is detected in activated T-cells where expression levels are 30- to 50-fold less than CD28 on the cell surface following activation. Mutations in CTLA4 gene is associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.  Alternate transcriptional splice variants, encoding different isoforms of CTLA4, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. The engineered CTLA4-Fc fusion proteins inhibit T-cell-dependent immune responses and are used as immunosuppressive agents by acting as a competitive inhibitor of CD28. Blockade of CTLA4 inhibitory activity with monoclonal antibodies enhances antitumor immunity and has been proven to be an effective approach for cancer immunotherapy. 

 

Product Details

 

Gene Symbol: CTLA4; CD152; CD; GSE; GRD4; CTLA-4; IDDM12; CELIAC3

 

NCBI Gene ID: 12477

 

Uniprot Entry: P09793

 

Construct Details: The recombinant mouse CTLA4-Fc is expressed as a 354-amino acid protein consisting of  Glu36 - Asp161 region of CTLA4 and a C-terminal Fc from human IgG1, which exists as a dimer under non-reducing conditions.  

 

Source: Mammalian cells stably expressing mouse CTLA4-Fc and growing in chemical-defined media with no animal components or antibiotics

 

Deduced Amino Acid Sequence: 

        10         20         30         40         50         60 

EAIQVTQPSV VLASSHGVAS FPCEYSPSHN TDEVRVTVLR QTNDQMTEVC ATTFTEKNTV 

        70         80         90        100        110        120 

GFLDYPFCSG TFNESRVNLT IQGLRAVDTG LYLCKVELMY PPPYFVGMGN GTQIYVIDPE 

       130        140        150        160        170        180 

PCPDSDSTGT HTCPPCPAPE LLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV 

       190        200        210        220        230        240 

KFNWYVDGVE VHNAKTKPRE EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE 

       250        260        270        280        290        300 

KTISKAKGQP REPQVYTLPP SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT 

       310        320        330        340        350 

TPPVLDSDGS FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 

  

M.W.: Calculated molecular mass (kDa): 39.4; Estimated by SDS-PAGE under reducing condition (kDa): 50-55

 

Calculated PI: 5.53

 

Calculated extinction coefficients (M-1 cm-1, at 280nm):  40975

 

Purity: >95% judged by SDS-PAGE under reducing condition (see the gel image above, labeled as "S" and "M" for marker)

 

Formulation: Supplied at 0.5 mg/ml in sterile PBS pH7.4 (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

 

 

  

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.

 

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. Eur. J. Immunol. 18:1901-1905 (1988)

2. J. Exp. Med. 174:561-569 (1991)

3. Annu. Rev. Immunol. 24:65-97 (2006)

4. Immunol. Rev. 229:307-321 (2009) 

 

 

 

 

Additional supporting documents, including PDS, 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.