CTLA-4 and CD80/CD86 Pathway

introduction to CTLA-4 and CD80/CD86 Pathway

T cell activation is efficient for cellular and humoral immune responses. This process helps the development of high-affinity antibody generation and cytotoxic T cell responses. However, the T cell activation must be tightly controlled to avoid autoimmunity. With the improved understanding of self-tolerance, a series of proteins have been identified to control T cell activation.

CTLA-4 is the transmembrane protein membrane of the immunoglobulin gene superfamily predominantly expressed on activated T cells. On the contrary, CD28 is always found on the surface of resting T cells. The low expression level of CTLA-4 on the cell surface is due to its rapid internalization by a clathrin pit mechanism. There are two natural ligands CD80 and CD86, for CD28/CTLA-4 receptor interactions. They are only approximately 25% identical in sequence and can both interact with CD28/CTAL-4. CD80 and CD86 can be found on various antigen-presenting cells, including monocytes, dendritic cells, and activated B cells. Some studies have shown that CD28 is highly expressed but with low affinity, while CTLA-4 is low abundance but with higher affinity.

Research and Drugs for CTLA-4 and CD80/CD86 Pathway

It has been proved that blocking CTLA-4 enhances T cell proliferation. It is interesting that both CD28 and CTLA-4 interact with the same ligands but have opposite effects. The most important model showed that low levels of ligands result in stronger competitive binding of CTLA-4 compared to CD28. In addition, CTLA-4 can interfere with TCR-derived signals and block early signaling events. Nowadays, a series of drugs targeting CTLA-4 and CD80/CD86 pathways have been discovered.

Fig.1 A schematic diagram of CD28 and CTLA-4 interactions with their ligands is depicted. (Sansom, 2000)

Services at Creative Biolabs

Creative Biolabs is a leading service provider that focuses on immune checkpoint inhibitors (ICIs) discovery. Based on our extensive experience on CTLA-4 and CD80/CD86 pathway, now we can provide a series of services for our clients all over the world, which include but are not limited to:

• Custom Immune Checkpoint Protein Development
• Antibody Development for Immune Checkpoints
• Immune Checkpoint Targeted Peptide Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Biomarker Development for Immune Checkpoint Inhibitor (ICI)
• Immune Checkpoint Assays
• Preclinical Research for Immune Checkpoint Targeting Drugs

If you are interested in our services, please do not hesitate to contact us for more detailed information.

Reference

1. Sansom, D. M. CD28, CTLA-4 and their ligands: who does what and to whom? Immunology. 2000, 101(2): 169.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.