Document Type : Review article
Authors
1
MSc. Department of Hematology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2
MSc. Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
3
Assistant professor of immunology, Immunology Research Center, Bu‐Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Assistant professor of immunology, Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract
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.
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