Highly efficient peptide binding and T cell activation by MHC class II molecules of CIITA-transfected cells

Abstract

Expression of MHC class II, DM and Ii genes is controlled by the transactivator CIITA, a mediator of the activation of these genes by IFN-gamma. Surprisingly, MHC class II molecules expressed on CIITA transfectants behave very differently from those expressed at the same level on IFN-gamma-induced cells in terms of peptide binding and peptide-specific T cell activation. MHC class II-positive CIITA transfectants exhibit an unusually high capacity for binding exogenous peptides, with a higher percentage of DR molecules occupied by a given peptide and are much more efficient at peptide-specific, HLA-DR-restricted activation of T lymphocytes. This unexpected phenotype reflects the antigen processing defect observed in CIITA transfectants. It suggests novel strategies for the use of CIITA-transformed cells in peptide-based immunization.