Molecular interactions between CTLA-4 and CD80/CD86 in the regulation of immune responses: a review article

One of the main mechanisms of regulating immune responses is the interaction between CTLA-4 and CD80/CD86. CTLA-4 is an inhibitory receptor and has the same ligand as co-stimulatory receptors CD28, CD80/86. CTLA-4 endocytosis these ligands through a process called trans-endocytosis and drives these ligands out of reach of the immune system stimulation. As a result, such a mechanism prevents the excessive response of the immune system. However, trans-endocytosis is performed only in the presence of one ligand. In this review, we investigated the interaction between CTLA-4 and CD80/CD86 and the importance of the presence of two distinct ligands for CTLA-4. This study represents that there is an opposite but necessary interaction between CD80 and CD86 with CTLA-4. In such a way, CD80 attenuates CTLA-4 functions and increases CD28-CD86 interaction by protecting CD86 from endocytosis, so CD28-CD86 interaction increases immune system stimulation. While CD86 enhances the inhibitory functions of CTLA-4. On the other hand, these interactions balance the inhibitory and the stimulatory functions of the immune system. Although CTLA-4 controls CD86, it is itself controlled by CD80, hence is prevented the over-inhibitory function of CTLA-4. Such a function arises only in the presence of both ligands. The present study provides a more obvious perception of the CTLA-4-CD80/86 regulatory system and the interactions between them.