Distinct patterns of membrane microdomain partitioning in Th1 and th2 cells.

Here we show that activated Th1 and Th2 cells have distinct patterns of membrane compartmentalization into lipid rafts. TCR complex members are recruited efficiently to rafts and aggregate with rafts at the site of MHC/peptide contact in Th1 cells but not Th2 cells. TCR/raft association in Th1 cells is deficient in the absence of CD4, suggesting that CD4 aids recruitment of the TCR to rafts. We show differential utilization of rafts in Th1 and Th2 cells by cholesterol depletion studies, which alters calcium signaling in Th1 but not Th2 cells. Furthermore, Th2 cells have a decreased ability to respond to low-affinity peptide stimulation. These studies indicate that components of membrane microdomains are differentially regulated in functionally distinct CD4 T cells.