MHC class II antigen presentation pathway in murine tumours: tumour evasion from immunosurveillance?

Br J Cancer. 2000 Nov;83(9):1192-201. doi: 10.1054/bjoc.2000.1415.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • H2-M antigens
  • HLA-D Antigens
  • HLA-DM antigens
  • Histocompatibility Antigens Class II
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Trans-Activators
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma