CTLA-4 Products

Description

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), also known as CD152, is a cell surface glycoprotein belonging to the immunoglobulin family with a role in regulation of T cell activation (1). Human CTLA-4 is a 223 amino acid (aa) protein with a theoretical molecular weight of 24.6 kDa containing a leader peptide, a IgV-like domain, a transmembrane domain, and a cytoplasmic tail (1,2). CTLA-4 is both structurally and functionally related with another member of the immunoglobulin-related receptor family, CD28 (1-3). CTLA-4 and CD28 receptors are both expressed by CD4+ and CD8+ T cells and share two common ligands, CD80 (B7.1) and CD86 (B7.2), expressed on the surface of antigen presenting cells (APCs) (2,3). While CD28 is present on the plasma membrane of T cells, CTLA-4 is predominantly expressed intracellularly on vesicles in FoxP3+ regulatory T (Treg) cells and activated T cells due to endocytosis (3). While they share ligands, the two receptors have opposing functions in T cell activation; CD28 is involved in activation of T cells, while CTLA-4 functions as a negative regulator of T cell response (2,3). One of the primary functions of CTLA-4 is preventing autoimmunity (1-4).

Similar to programmed cell death protein 1 (PD-1), CTLA-4 is an inhibitory immune checkpoint protein (3,5). Checkpoint blockade immunotherapy using drugs or antibodies to target CTLA-4 is one of the main approaches for cancer treatment (5). A number of drugs targeting CTLA-4, or a combination of CTLA-4/PD-1, have been approved for treatment of various cancers like melanoma, renal cell carcinoma, and colorectal cancer (5). While blocking CTLA-4 in the tumor microenvironment is a promising cancer therapeutic, the absence of CTLA-4 under normal conditions can have deleterious effects. Studies have found that patients with CTLA-4 deficiency or mutations have clinical features associated with autoimmunity and immune dysregulation (4). Treatment options for CTLA-4 deficiency includes immunoglobulin-replacement therapy, corticosteroids, CTLA-4-immunoglobulin (Ig) fusion protein, and, in life-threatening cases, hematopoietic stem cell transplantation (4,6). Additionally, engaging CD80/CD86 with CTLA-4-Ig is a common immunosuppressive treatment for rheumatoid arthritis and kidney transplant recipients (6).

References

1. Romo-Tena, J., Gomez-Martin, D., & Alcocer-Varela, J. (2013). CTLA-4 and autoimmunity: new insights into the dual regulator of tolerance. Autoimmunity reviews, 12(12), 1171-1176. https://doi.org/10.1016/j.autrev.2013.07.002

2. Hosseini, A., Gharibi, T., Marofi, F., Babaloo, Z., & Baradaran, B. (2020). CTLA-4: From mechanism to autoimmune therapy. International immunopharmacology, 80, 106221. https://doi.org/10.1016/j.intimp.2020.106221

3. Rowshanravan, B., Halliday, N., & Sansom, D. M. (2018). CTLA-4: a moving target in immunotherapy. Blood, 131(1), 58-67. https://doi.org/10.1182/blood-2017-06-741033

4. Verma, N., Burns, S. O., Walker, L., & Sansom, D. M. (2017). Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations. Clinical and experimental immunology, 190(1), 1-7. https://doi.org/10.1111/cei.12997

5. Rotte A. (2019). Combination of CTLA-4 and PD-1 blockers for treatment of cancer. Journal of experimental & clinical cancer research : CR, 38(1), 255. https://doi.org/10.1186/s13046-019-1259-z

6. Bluestone, J. A., St Clair, E. W., & Turka, L. A. (2006). CTLA4Ig: bridging the basic immunology with clinical application. Immunity, 24(3), 233-238. https://doi.org/10.1016/j.immuni.2006.03.001

Bioinformatics

Entrez	12477 Mouse 1493 Human 63835 Rat
Uniprot	NM_005214 Human NP_005205 Human P09793 Mouse P16410 Human Q6GR94 Human
Product By Gene ID	1493
Alternate Names	CD CD152 antigen CD152IDDM12 CD28 celiac disease 3 CELIAC3 CTLA-4 cytotoxic T-lymphocyte antigen 4 cytotoxic T-lymphocyte protein 4 Cytotoxic T-lymphocyte-associated antigen 4 cytotoxic T-lymphocyte-associated protein 4 cytotoxic T-lymphocyte-associated serine esterase-4 GRD4 GSE ICOS ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4

Research Areas for CTLA-4

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Signal Transduction

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