Suppression of MHC class II expression by human class II trans-activator constructs lacking the N-terminal domain.
The class II trans-activator (CIITA) is a bi- or multi-functional domain protein which plays a critical role in the expression of MHC class II genes. We report that removal of the N-terminal 151 amino acids, encompassing all of the acidic domain but leaving intact the proline/serine/threonine-rich domain, results in a mutant protein with potent suppressive properties for MHC class II expression. HeLa cells stably or transiently transfected with mutant CIITA constructs showed up to 99% suppression of MHC class II antigen induction by IFN-gamma and marked suppression of HLA-DRA mRNA expression. Transient transfection of a B lymphoma line resulted in up to 89% reduction of constitutive MHC class II expression within 5 days and suppression of HLA-DRA mRNA synthesis.
Yun
S
S
Division of Cell and Molecular Biology, University College London Medical School, UK.
Gustafsson
K
K
Fabre
J W
JW
D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D005802:Genes, MHC Class II; D005822:Genetic Vectors; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D014162:Transfection
D017931:DNA Primers; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma