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Walter, W, Lingnau, K, Schmitt, E, Loos, M and Maeurer, MJ (2000) MHC class II antigen presentation pathway in murine tumours: tumour evasion from immunosurveillance? Br. J. Cancer 83:1192-201
Qualitative differences in the MHC class II antigen processing and presentation pathway may be instrumental in shaping the CD4+ T cell response directed against tumour cells. Efficient loading of many MHC class II alleles with peptides requires the assistance of H2-M, a heterodimeric MHC class II-like molecule. In contrast to the HLA-DM region in humans, the beta-chain locus is duplicated in mouse, with the H2-Mb1 (Mb1beta-chain distal to H2-Mb2 (Mb2) and the H2-Ma (Ma) alpha-chain gene). Here, we show that murine MHC class II and H2-M genes are coordinately regulated in murine tumour cell lines by T helper cell 1 (IFN-gamma) and T helper cell 2 (IL-4 or IL-10) cytokines in the presence of the MHC class II-specific transactivator CIITA as determined by mRNA expression and Western blot analysis. Furthermore, Malphabeta1 and Malphabeta2 heterodimers are differentially expressed in murine tumour cell lines of different histology. Both H2-M isoforms promote equally processing and presentation of native protein antigens to H2-A(d)- and H2-E(d)-restricted CD4+ T cells. Murine tumour cell lines could be divided into three groups: constitutive MHC class II and CIITA expression; inducible MHC class II and CIITA expression upon IFN-gamma-treatment; and lack of constitutive and IFN-gamma-inducible MHC class II and CIITA expression. These differences may impact on CD4+ T cell recognition of cancer cells in murine tumour models.
Animals; Antigen Presentation; Blotting, Western; CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/immunology; Dimerization; Gene Expression Regulation, Neoplastic/drug effects; HLA-D Antigens/chemistry; HLA-D Antigens/genetics; HLA-D Antigens/metabolism; Histocompatibility Antigens Class II/genetics; Histocompatibility Antigens Class II/immunology; Interferon-gamma/pharmacology; Interleukin-10/pharmacology; Interleukin-4/pharmacology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nuclear Proteins; Protein Isoforms/chemistry; Protein Isoforms/genetics; Protein Isoforms/metabolism; RNA, Messenger/drug effects; RNA, Messenger/genetics; RNA, Messenger/metabolism; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Trans-Activators/genetics; Tumor Cells, Cultured/drug effects; Tumor Cells, Cultured/immunology; Tumor Cells, Cultured/metabolism
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