Figure 1.
T-cell regulation, CTLA-4, and Ipilimumab. A) Normal T-cell activation occurs via presentation of MHC-bound antigens on APCs that signal through the TCR. This process is amplified by the co-stimulatory signal produced by interaction of the CD80/86 (B7) receptor on APCs with CD28 molecules on the T-cell. Prolonged T-cell activation initiates the upregulation of CTLA-4, a membrane receptor that competes with CD28 for binding to CD80/86 (B7). CTLA-4 has a higher affinity for CD80/86 (B7) than CD28 and its binding oppositely produces inhibitory signals through decreased proliferation and IL-2 production. This relationship allows normal T-cells to prevent over-activation through feedback upregulation of CTLA-4. B) Ipilimumab binds to CTLA-4 and prevents interaction with CD80/CD86 (B7) molecules on APCs. This removes CTLA-4 induced inhibitory signals allowing for unregulated and prolonged activation of T-cells in a non-specific manner.