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

Qualitative differences in the MHC class II antigen processing and presenta tion pathway may be instrumental in shaping the CD4+ T cell response direct ed against tumour cells. Efficient loading of many MHC class II alleles wit h peptides requires the assistance of H2-M, a heterodimeric MHC class II-li ke molecule. In contrast to the HLA-DM region in humans, the beta -chain lo cus is duplicated in mouse, with the H2-Mb1 (Mb1 beta -chain distal to H2-M b2 (Mb2) and the H2-Ma (Ma) alpha -chain gene). Here, we show that murine M HC 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) c ytokines in the presence of the MHC class II-specific transactivator CIITA as determined by mRNA expression and Western blot analysis. Furthermore, M alpha beta1 and M alpha beta2 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 divi ded into three groups: constitutive MHC class II and CIITA expression; indu cible 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 i n murine tumour models. (C) 2000 Cancer Research Campaign.