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. 2023 Jul 11;14:1198365. doi: 10.3389/fimmu.2023.1198365

Figure 1.

Figure 1

Signaling pathway of T-cell activation and CTLA-4 surface expression. Two signals are essential for T-cell activation. One is TCR-MHC signaling and another one is CD28-CD80/86 co-stimulation. After successful co-stimulation, naïve T cells become active and perform their function. After activation, T cells expresses CTLA-4 and CTLA-4 binds with CD80/86 molecules and functionally inactivated T cell (left panel). The newly synthesized CTLA-4 binds with TRIM in the TGN and comes out on the cell surface. PLD and ARF-1 are also responsible for externalization of CTLA-4. On the other side, CTLA-4 binds with CAP-1 and directs transport to lysosomal compartment. From the surface, dephosphorylated tyrosine 201 of CTLA-4 binds with clathrin adaptor protein-2 (CAP-2) and transports endosome to lysosome (right panel). APC, Antigen-presenting cell; TCR, T-cell receptor; MHC, Major histocompatibility complex; CTLA-4, Cytotoxic T lymphocyte antigen 4; CD28, TRIM, Transmembrane adaptor T-cell receptor interacting molecule; TGN, Trans Golgi network; PLD, Phospholipase D; ARF-1, GTPase ADP ribolysation factor-1; CAP-1, Clathrin adaptor protein-1; CAP-2, Clathrin adaptor protein-2.