CD28 AFFECTS THE EARLIEST SIGNALING EVENTS GENERATED BY TCR ENGAGEMENT

The efficiency and magnitude of T cell responses are influenced by lig ation of the costimulatory receptor CD28 by B7 molecules expressed on antigen-presenting cells (APC). In contrast to most previous studies i n which agonistic anti-TCR/CD3 and anti-CD28 antibodies were employed, here we have investigated the contribution of CD28 to T cell activati on under physiological conditions of antigen presentation. Jurkat T ce lls and primary T cells from TCR-transgenic mice stimulated with super antigen and antigen, respectively, presented by B7-expressing APC were utilized. In both systems we show that inhibiting CD28/B7 interaction resulted in impaired TCR-induced tyrosine phosphorylation of the sign al-transducing zeta chain and ZAP-70. Consistent with a blockade of TC R-proximal signaling events, Jurkat cells stimulated in the absence of CD28 ligation were found to have strongly diminished tyrosine phospho rylation of cellular substrates and downstream signaling pathways such as Ca2+/calcineurin, ERK/MAPK and JNK. Our results provide evidence f or a role of CD28 in enhancing TCR signaling capacity during the earli est stages of T cell:APC interaction.