Monday, 6 November 2017

CTLA-4 (CD152)

The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or cluster of differentiation 152 (CD152), is a receptor on activated T cells that, functioning as an immune checkpoint, downregulates immune responses. It is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation. It acts as an off switch when bound to CD80 or CD86 on the surface of antigen-presenting cells [2]. It binds B7 molecules with a higher affinity than CD28, downregulating T-cell responses by inhibiting CD28 signaling [1].
CD80/CD86 are members of the immunoglobulin superfamily and present on mature antigen-presenting cells. They share their ligands (CD28 and CTLA-4) on T cells and play a major role as costimulatory molecules in the major histocompatibility complex class II-mediated peptide antigen presentation [1].
B7 molecules are a family of cell-surface proteins that function as costimulatory molecules transducing second signals for T cell-dependent immune responses [1].
CD28 is an activating receptor for B7 molecules present on naive T cells. The interaction of CD28 with B7 molecules provides the costimulatory or second signal for T-cell activation [1].
«(...) there is increasing interest in the possible therapeutic benefits of blocking CTLA-4 (using antagonistic antibodies against CTLA such as ipilimumab (FDA [Food and Drug Administration] approved for melanoma in 2011) as a means of inhibiting immune system tolerance to tumours and thereby providing a potentially useful immunotherapy strategy for patients with cancer» [2].
Bibliographic references:
[1] Tortora, G., Bergmann, L., Lindh, M., Cervantes-Ruiperez, A., Dziadziuszko, R., Eckhardt, S., Lenz, H., Normanno, N., Perez, D., Scarpa, A., Syrigos, K., Tabernero, J. and Troiani, T. (2014). ESMO glossary in molecular biology of cancer. Viganello-Lugano, Switzerland: European Society for Medical Oncology.
[2] CTLA-4. Enwikipediaorg. 2017. Available at: Accessed November 6, 2017.