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Highly efficient peptide binding and T cell activation by MHC class II molecules of CIITA-transfected cells
E Martinez-Soria1, C A Siegrist, B Mach
1L. Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
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.
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.