MHC Class I Molecules Are Implicated in Costimulatory Signals during TCR/CD3-Induced Activation

Mouse MHC class I-specific mAbs recognizing the α1/α2, but not those directed against the α3 domain of the molecule, inhibited RNA, protein, and DNA synthesis of splenic T cells in response to stimulation through the TCR/CD3 complex. Similar inhibition was seen with LFA-1-specific mAbs under the same stimulation conditions. The effect of class I- and LFA-1-specific mAbs reflected a decrease of both IL-2 and IFN-γ synthesis and IL-2 receptor α chain induction. IL-2, IL-2 receptor α chain, IFN-γ, c-fos,c-jun,and c-mycmRNAs were not detected. Activation of AP-1 (c-Fos and c-Jun proteins) and NF-κB transcription factors were also inhibited. Inhibition was observed both after treatment of cells in culture and after intravenous injection of Abs in mice. Although bulk phosphorylation was inhibited, early tyrosine phosphorylation and calcium ion influx were normally induced. Protein phosphatase inhibitors did not reverse this inhibition, ruling out an enhanced activation of these enzymes in the observed inhibition. Cell surface expression of one of early PKC activation marker, CD69 was also inhibited. Phorbol esters that directly activate PKC prevented inhibition. Thus, class I molecules are implicated in signal transduction involved at an early stage for T cell activation in a manner that suggests their implication in accessory signal transmission that contributes to the regulation of PKC activity.