CTLA4 Signaling

CTLA4 is sequestered inside intracellular vesicles in resting T cells but is mobilized to the cell surface when T cells become activated by antigen presenting cells (APCs). On the cell surface, CTLA4 competes with CD28 to bind CD80 and CD86, co-stimulatory proteins on APCs that deliver the secondary activation signal to T cells when they engage CD28. When CD80 and CD86 bind CTLA4, however, inhibitory signals are initiated in the T cell, resulting in PP2A and SHP2-mediated dephosphorylation of signaling proteins recruited to the TCR complex. These inhibitory processes stop the T cell from becoming activated. In T regulatory cells (Tregs), CTLA4 is constitutively expressed on the cell surface, and blocks activation of nearby T cells by occupying CD80 and CD86 on APCs so that they are unable to bind CD28 on other T cells.

 

Click on the poster below to view the interactive version.