CTLA4 is one of the best studied inhibitory receptors of the CD28 superfamily. CTLA4 inhibits T cell activation by reducing IL2 production and IL2 expression, and by arresting T cells at the G1 phase of the cell cycle. CTLA-4 expressed by a T cell subpopulation exerts a dominant control on the proliferation of other T cells, which limits autoreactivity. CTLA4 also blocks CD28 signals by competing for the ligands B71 and B72 in the limited space between T cells and antigenpresenting cells. Though the mechanism is obscure, CTLA4 may also propagate inhibitory signals that actively counter those produced by CD28. CTLA4 can also function in a ligand-independent manner.CTLA-4 regulates the activation of pathogenic T cells by directly modulating T cell receptor signaling (i.e. TCR-zeta chain phosphorylation) as well as downstream biochemical signals (i.e. ERK activation). The cytoplasmic region of CTLA4 contains a tyrosine motif YVKM and a proline rich region. After TCR stimulation, it undergoes tyrosine phosphorylation by src kinases, inducing surface retention.
Yates, JR, Becart, S, Saito, T, Casas, J, Canonigo-Balancio, AJ, Kronenberg, M, Kong, KF, Gascoigne, NR, Yokosuka, T, Kim, G, Altman, A, Fu, G, Zhang, Y
Frauwirth, KA, Alegre, ML, Thompson, CB
Hoefen, RJ, Berk, BC
Madrenas, J, Teft, WA, Kirchhof, MG
Schneider, H, Rudd, CE
Hutchcroft, JE, Slavik, JM, Bierer, BE
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