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. 2023 Aug 24;14:1212476. doi: 10.3389/fimmu.2023.1212476

Figure 1.

Figure 1

Structure and biological activities of CTLA-4. As homolog of CD28, CTLA-4 possesses the same structure and shares the same ligands B7, CD80 (B7-1) and CD86 (B7-2). CTLA-4 is a divalent dimer, which contains two binding sites, whereas CD28 is a monovalent (which contains a single binding site) dimer. Although both belong to the B7 family, CD80 is a divalent dimer and CD86 is a monomer. CTLA-4 is predominantly present in the intracellular vesicles of T cells, which is due to the constitutive clathrin-dependent endocytosis of CTLA-4 from the plasma membrane, resulting in 90% of CTLA-4 being intracellular. Endocytosis of CTLA-4 is related to the dephosphorylation of its YVKM motif, once CTLA-4 is dephosphorylation, clathrin adapter AP-2 binds to GVYVKM motif of CTLA-4, rapidly inducing internalization. In the TGN, newly synthesized CTLA-4 binds to the transmembrane adapter TRIM, which promotes the formation of CTLA-4-containing vesicles and their transport to the cell surface. CTLA-4, Cytotoxic T-lymphocyte antigen 4; APC, antigen-presentation cell; TGN, trans-Golgi network; TRIM, TCR-interacting molecule; AP-2, μ2 subunit of the clathrin adaptor protein complex.