Abstract

Signaling through MHC class II molecules can lead to either cell activation or death. This can be accomplished through activation of two distinct signaling pathways—one involves a Src-independent activation of PKCβ that we coupled to the induction of cell death, and another involves activation of Src kinases that has been coupled to cell activation. These two MHC class II-mediated signaling pathways originate from different location in the plasma membrane—PKCβ activation is mediated through MHC class II molecules outside rafts whereas Src kinase activation is mediated through them inside rafts. Whether inside or outside rafts, these molecules mediate activation of various signaling pathways through their associations with other receptors, as evidenced by our description of HLA-DR/CD18 complex in monocytes. Finally, the allelic polymorphism of MHC class II may, indeed, present the molecular basis that create differential associations with other cell surface receptors and/or protein-membrane compartment interactions, and consequently differential MHC class II-mediated responses.