Critical Requirement for the Membrane-Proximal Cytosolic Tyrosine Residue for CD28-Mediated Costimulation In Vivo

摘要: The YMNM motif that exists in the CD28 cytoplasmic domain is known as a binding site for phosphatidylinositol 3-kinase and Grb-2 considered to be important CD28-mediated costimulation. To address role of cosignaling primary T cells, we generated transgenic mice on null background express mutant lacking ability Grb-2. After anti-CD3 anti-CD28 Ab stimulation vitro, initial proliferative response IL-2 secretion Y189F cells were severely compromised, while later responses intact. In contrast stimulation, PMA failed induce production from at any time point. Using graft-vs-host reaction system, assessed costimulation vivo found spleen engraft could not acute reaction. Together, these results suggest membrane-proximal tyrosine required vivo. Furthermore, indicate vitro assays may always correlate with cell activation