Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III.
Activated human T cells express HLA-DR, HLA-DQ, and HLA-DP on their surface, but the regulation and functioning of MHC class II molecules in T lymphocytes are poorly understood. Because the MHC class II transactivator (CIITA) is essential for MHC class II expression, we have investigated transcriptional activation of CIITA in activated T cells. In this study, we show that in human activated CD4(+) T cells, CIITA promoter III (CIITA-PIII) drives the expression of CIITA. The in vivo genomic footprint analysis revealed activated T cell-specific occupation of CIITA-PIII. Subsequent EMSA analysis of several promoter regions showed differences in banding pattern among activated T cells, naive T cells, primary B cells, and Raji B cells. Activating response element (ARE)-1 is shown to interact with the acute myeloid leukemia 2 transcription factor in nuclear extracts derived from both T and B cells. Interestingly, the acute myeloid leukemia 3 transcription factor was bound in nuclear extracts of T cells only. The ARE-2 sequence is able to bind CREB/activating transcription factor family members in both T and B cells. In addition, a yet unidentified Ets family member was found to interact with site C in activated T cells, whereas in B cells site C was bound by PU.1 and Pip/IFN regulatory factor 4/IFN consensus sequence binding protein for activated T cells. In Jurkat T cells, both ARE-1 and ARE-2 are crucial for CIITA-PIII activity, similar to Raji B cells. The differential banding pattern in in vivo genomic footprinting and transcription factor binding at the ARE-1 and site C between T cells and B cells probably reflects differences in CIITA-PIII activation pathways employed by these cell types.
Holling
Tjadine M
TM
Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
van der Stoep
Nienke
N
Quinten
Edwin
E
van den Elsen
Peter J
PJ
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000276:immunology*; D020218:Response Elements / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators