Abstract:T cell activation requires signaling through the TcR and engagement of a costimulatory receptor. CD28 is the most important costimulatory receptor; however, the signaling pathways initiated by CD28 remain highly controversial. To examine this, we generated gene targeted knock-in mice that express mutations in either the 1) proximal YMNM (Y170F), 2) distal PYAP (AYAA), or 2) both the YMNM and PYAP (Y170F/AYAA) motifs of the cytoplasmic tail of CD28. Mutation of the PYAP motif resulted in impaired proliferation,… Show more
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