Table 1.

Immune checkpoints involved in viral infections and their T-cell inactivation pathways.

Immune Checkpoint	Super Family	Ligand	Expression	T-cell Inactivation Pathway	Ref.
PD-1	CD28	PD-L1/L2	T-cells, B-cells, natural killer T-cells, DCs and activated monocytes	(1)PD-1(ITSMs) → SHP2 → ZAP70/LCK → Ras-MEK-MAPK →AP1 (2)PD-1(ITSMs) → SHP2 → PI3K/AKT →NFAT	[20,21,22]
CTLA-4	CD28	B7 (CD80/CD86)	Active T-cells	CTLA-4 → PP2A → Akt → mTORc1 → regulates T-cell proliferation and differentiation	[25,26,27]
TIM-3	TIM	Galcetin-9	Th1, Tc1, Treg cells	(1)TIM-3 → release Bat3 → LCK / FYN → ZAP70 → Ras-MEK-MAPK → AP1 (2)TIM-3 → release Bat3 → LCK / FYN → ZAP70 → PLC-γ → NFAT	[32]
TIGIT	CD28	CD155 on DCs	T-cells and NK cells	TIGIT → SHIP1 → PI3K → AKT/PKC/IKK → NF-κB	[31,35]
LAG-3	Immunoglobulin	MHC class Ⅱ	Activated T-cells Treg cells, B-cells, DCs and NK cells	LAG- KIEELE motif /FXXL motif/ C terminus EX repeat → unknown	[38]
BTLA/CD160	CD28	HVEM	T-cells and B-cells, activated T-cells	(1)BTLA(ITIM/ITSM) → SHP-1/2 → LCK / FYN → ZAP70 → Ras-MEK-MAPK → AP1 (2)BTLA(ITIM/ITSM) → SHP-1/2 → LCK / FYN → ZAP70 → PLC-γ → NFAT	[39,41]