CTLA-4 Negative Signaling via Lipid Rafts: A New Perspective

Proper function of the immune system requires that activation of T cells is precisely regulated. Responses to the T cell receptor are modulated by signals from other receptors. CTLA-4 (cytotoxic T lymphocyte antigen-4, also called CD152), for example, inhibits cytokine production and proliferation of T cells. Activation of T cells is associated with the accumulation of signaling proteins in lipd rafts--microdomains of the plasma membrane enriched in cholesterol and glycosphingolipds. Rudd et al. discuss evidence that CTLA-4 might inhibit cytokine production and T cell proliferation by limiting the assembly of lipid rafts, which are critical to the formation of a functional immunological synapse between antigen-presenting cells and T cells.