The role of lipid rafts or glycosylphosphatidylinositol (GPI)- domains has been reported to be very important during T cell activation via clustering important molecular players, such as adhesion molecules, GPI-anchored proteins or signaling kinases. The main focus of my study is to explore the role of GPI-anchored proteins in activation of T cells. We have previously found that the GPI-anchored molecules, CD48 and CD59 behave differentially. Since CD2 has been shown to interact with CD48 in cis and trans configuration, I asked whether this interaction could be responsible for the differential behavior of CD48 and CD59. For this purpose I used the siRNA technology and down regulated CD2 and CD48 expression in Jurkat T cells. The knock- out cells showed altered recruitment of Lck, a Src family kinase (SFK) member, and LAT, a transmembrane adaptor protein (TRAP), to the TCR/CD3, decreased IL-2 promoter activity and decreased calcium flux as compared with the normal cells. Thus, these results show that CD2 and CD48 are not only important for recruitment of Lck and LAT but that they also interplay for association of these molecules and proper signal transduction.