HLA CLASS-II MOLECULES TRANSDUCE ACCESSORY SIGNALS AFFECTING THE CD3 BUT NOT THE INTERLEUKIN-2 ACTIVATION PATHWAY IN T-BLASTS

MHC class II molecules play a central role in the control of the immun e response, but their biologic function and mechanism of action on the surface of activated human T lymphocytes are not entirely understood. In our study, the functional role of HLA class II molecules in T-blas t proliferation was investigated by analyzing in parallel the IL-2- an d CD3-driven activation pathways. The results indicate that the cross- linking of class II and CD3 molecules significantly increased the CD3- mediated T-blast proliferation, while no effect was observed on the IL -2-driven cell activation. This phenomenon was not confined to either CD4(+) or CD8(+) subsets nor was specifically affected by CD45 trigger ing. Biochemical studies showed that signaling via MHC class II molecu les in T blasts led to PKC membrane translocation and IP accumulation. The simultaneous triggering of CD3 and HLA class II molecules led to a synergistic effect on IP accumulation but did not increase the CD3-m ediated PKC membrane translocation. Our data suggest that HLA class II molecules are involved in T-cell-T-cell interactions and can mediate accessory signals, affecting the T-lymphocyte activation state.