Cutting edge: distinct motifs within CD28 regulate T cell proliferation and induction of Bcl-XL

CD28 provides an important costimulatory signal in T cell ac-tivation that regulates multiple cellular processes including proliferation and survival. Several signal transduction path-ways are activated by CD28; however, the precise biochemical mechanism by which CD28 regulates T cell function remains controversial. Retroviral gene transfer into primary T cells from TCR-transgenic, CD28-deficient mice was used to deter-mine the specific sequences within CD28 that determine func-tion. Discrete regions of the cytoplasmic domain of CD28 were identified that differentially regulate T cell proliferation and induction of the anti-apoptotic protein Bcl-XL. Mutation of C-terminal proline residues abrogated the proliferative and cy-tokine regulatory features of CD28 costimulation while pre-serving Bcl-XL induction. Conversely, mutation of residues important in phosphatidylinositol 3-kinase activation partiall