Description
B7-2, also referred to as CD86, is a glycosylated type 1 membrane protein that is a member of the immunoglobulin (Ig) superfamily (1). B7-2/CD86 is constitutively expressed on antigen presenting cells (APCs) such as dendritic cells (DCs), macrophages, and B cells and functions in controlling immune responses through either costimulatory or coinhibitory signals (1,2). Expression of B7-2 is upregulated by APCs upon activation and can be induced in T cells (1,3). The human B7-2 protein, encoded by the CD86 gene, is 329 amino acids (aa) in length with a theoretical molecular weight (MW) of 37.6 kDa (4). The B7-2 protein contains characteristic Ig variable-like (IgV) and constant-like (IgC) domains within its extracellular region (1,3). B7-2/CD86 has structural similarity and shares ~25% sequence homology with another B7 family molecule, B7-1/CD80 (3,5). Both B7-1 and B7-2 are ligands for the activating receptor CD28 and the regulatory receptor cytotoxic T-lymphocyte antigen 4 (CTLA-4) which are expressed on subsets of T cells (1-3,5-7). However, B7-1 and B7-2 bind to CTLA-4 with higher affinity than CD28 (3,5,6). B7-2/CD86 binding to CD28 results in costimulatory signals to promote T cell activation, proliferation, and cytokine production (1-3. 5-7). Binding to CTLA-4 initiates coinhibitory signaling to attenuate the pro-inflammatory T cell response, while also promoting the suppressive function of regulatory T (Treg) cells through expression of indoleamine 2,3-deoxygenase (IDO) (1-3,6,7). Molecules involved in T cell co-signaling have become considerable targets of interest for cancer immunotherapy (7). The anti-CTLA-4 monoclonal antibody ipilimumab, first approved for the treatment of metastatic melanoma, prevents B7-1/B7-2 molecules from binding to CTLA-4, thus driving B7-CD28 binding and promoting costimulatory signals and antitumor effects (1,7,8). Combination therapies targeting co-signaling molecules are currently under investigation to improve antitumor response for treatment of both melanoma and non-melanoma cancers (7,8).
References
1. Collins M, Ling V, Carreno BM. The B7 family of immune-regulatory ligands. Genome Biol. 2005;6(6):223. https://doi.org/10.1186/gb-2005-6-6-223
2. Greaves P, Gribben JG. The role of B7 family molecules in hematologic malignancy. Blood. 2013;121(5):734-744. https://doi.org/10.1182/blood-2012-10-385591
3. Bolandi N, Derakhshani A, Hemmat N, et al. The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment. Int J Mol Sci. 2021;22(19):10719. https://doi.org/10.3390/ijms221910719
4. Uniprot (P42081)
5. Bhatia S, Edidin M, Almo SC, Nathenson SG. B7-1 and B7-2: similar costimulatory ligands with different biochemical, oligomeric and signaling properties. Immunol Lett. 2006;104(1-2):70-75. https://doi.org/10.1016/j.imlet.2005.11.019
6. Ohue Y, Nishikawa H. Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?. Cancer Sci. 2019;110(7):2080-2089. https://doi.org/10.1111/cas.14069
7. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition [published correction appears in Nat Rev Immunol. 2013 Jul;13(7):542]. Nat Rev Immunol. 2013;13(4):227-242. https://doi.org/1010.1038/nri3405
8. Karimi A, Alilou S, Mirzaei HR. Adverse Events Following Administration of Anti-CTLA4 Antibody Ipilimumab. Front Oncol. 2021;11:624780. https://doi.org/101010.3389/fonc.2021.624780
Bioinformatics
Entrez |
Mouse Rat Human |
Uniprot |
Human Human Human Human |
Product By Gene ID |
942 |
Alternate Names |
- Activation B7-2 antigen
- B70
- B7-2 antigen
- B7-2
- B-lymphocyte activation antigen B7-2
- BU63
- CD28 antigen ligand 2
- CD28LG2B7-2 antigen)
- CD86 antigen
- CD86 molecule
- CTLA-4 counter-receptor B7.2
- FUN-1
- LAB72
- MGC34413
- T-lymphocyte activation antigen CD86
|