Trim modulation of CTLA-expression and function

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The immune system provides protection from opportunistic bacterial and viral infections. The regulation of T-cell activation is a critical step in the immune response. CD28 and CTLA-4 are cell surface molecules which play central roles in the regulation of T-cell function. While CD28 augments T-cell responses, CTLA-4 generates potent signals that dampen the immune response. The importance of CTLA-4 is demonstrated in mice lacking this receptor. They develop a massive lymphoproliferative disorder and die at an early age. In contrast to CD28, most of CTLA-4 is localized inside the cell. This application proposes to investigate how CTLA-4 is transported to the cell surface and controls T-cell responses.