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CTLA-4 & CD80 (CD86) Immune Checkpoint Pathway

CTLA-4 & CD80 (CD86) Immune Checkpoint Pathway: Description

Mechanisam of CTLA-4 & CD80 (CD86) immune checkpoint pathway
CTLA-4 / CD152, the first immune checkpoint receptor to be clinically targeted, is expressed exclusively on T cells where it primarily regulates the amplitude of the early stages of T cell activation. Although the exact mechanisms of CTLA-4 / CD152 action are under considerable debate, it has been proposed that its expression on the surface of T cells dampens the activation of T cells by outcompeting CD28 in binding CD80 / B7-1 and CD86 / B7-2. CD28 signalling strongly amplifies TCR signalling to activate T cells. CD28 and CTLA-4 / CD152 share identical ligands: CD80 / B7-1 and CD86 / B7-2. Besides, a number of studies suggest that activation of the protein phosphatases, SHP2 (also known as PTPN11) and PP2A, are important in counteracting kinase signals that are induced by TCR and CD28.

Functions of CTLA-4 & CD80 (CD86) immune checkpoint pathway
Even though CTLA-4 / CD152 is expressed by activated CD8+ effector T cells, the major physiological role of CTLA-4 & CD80 (CD86) Immune Checkpoint Pathway seems to be through distinct effects on the two major subsets of CD4+ T cells: downmodulation of helper T cell activity and enhancement of regulatory T (TReg) cell immunosuppressive activity. CTLA-4 / CD152 blockade results in a broad enhancement of immune responses that are dependent on helper T cells and, conversely, CTLA-4 / CD152 engagement on TReg cells enhances their suppressive function. CTLA-4 / CD152 is a target gene of the forkhead transcription factor FOXP3, the expression of which determines the TReg cell lineage, and TReg cells therefore express CTLA-4 / CD152 constitutively. Although the mechanism by which CTLA-4 / CD152 enhances the immunosuppressive function of TReg cells is not known, TReg cell-specific CTLA-4 / CD152 knockout or blockade significantly inhibits their ability to regulate both autoimmunity and antitumour immunity. Thus, in considering the mechanism of action for CTLA-4 / CD152 blockade, both enhancement of effector CD4+ T cell activity and inhibition of TReg cell-dependent immunosuppression are probably important factors.

CTLA-4 & CD80 (CD86) Immune Checkpoint Pathway: Reference

CTLA-4 & CD80 (CD86) Immune Checkpoint Pathway: Relatives

CTLA-4 & CD80 (CD86) Immune Checkpoint Pathway: Relatives

Co-inhibitory immune checkpoint pathways Co-stimulatory immune checkpoint pathways
PD1 & PD-L1 immune checkpoint pathway CD40 & CD40L immune checkpoint pathway
B7-H3 / CD276 immune checkpoint pathway OX40 & OX40L immune checkpoint pathway
B7-H4 / B7S1 / B7x immune checkpoint pathway HVEM & LIGHT immune checkpoint pathway
HVEM & BTLA immune checkpoint pathway CD28 & CD80 (CD86) immune checkpoint pathway
HVEM & CD160 immune checkpoint pathway GITR & GITR Ligand immune checkpoint pathway
LAG3 / CD223 / Lymphocyte activation gene 3 immune checkpoint pathway CD27 & CD70 immune checkpoint pathway
Galectin-9 & TIM-3 immune checkpoint pathway 4-1BB & 4-1BBL immune checkpoint pathway
Indoleamine 2,3-dioxygenase/IDO immune checkpoint pathway ICOS & ICOS Ligand immune checkpoint pathway
VISTA / B7-H5 / GI24 immune checkpoint pathway CD266 & CD155 immune checkpoint pathway
CEACAM1 / CD66a immune checkpoint pathway  
SIRP alpha & CD47 immune checkpoint pathway  
2B4 & CD48 immune checkpoint pathway  
TIGIT & CD155 immune checkpoint pathway  
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