Genetic analysis of CD28 signaling.

T cell activation is central to initiating an immune response. Two signals are required: an antigen-specific signal through the T cell receptor (TCR) and an antigen-independent costimulatory signal, primarily through CD28 in naïve T cells. Although many of the molecules involved in TCR signal transduction have been identified, the signaling pathways downstream of CD28 involved in costimulation are not well-defined. Through mutagenesis, we have generated a panel of Jurkat T cell lines in which CD28 costimulation fails to upregulate the RE/AP composite element of the IL-2 promoter. Biochemical analysis and genetic rescue of the defects in these cell lines will lead to a better understanding of CD28 signal transduction.