Analysis of the major histocompatibility complex class I antigen presentation machinery in normal and malignant renal cells: evidence for deficiencies associated with transformation and progression.

摘要: In some human tumors, reduced or defective MHC class I surface expression has been attributed to functional deficiencies of the genes antigen-processing machinery, proteasome subunits low molecular weight (LMP)-2 and LMP-7, as well peptide transporters associated with antigen processing (TAP)-1 TAP-2. Using normal epithelial kidney cells (MZ1851NN) renal cell carcinoma lines established from primary tumor (MZ1851RC) a lymph node metastasis (MZ1851LN) same patient, we investigated whether modulation antigens, TAP LMP molecules, occurs during transformation subsequent progression. The mRNA protein heavy light chain was strongly in MZ1851RC when compared corresponding MZ1851NN, this suppression even more pronounced metastatic line MZ1851LN. addition, activity measured by translocation assays, also markedly diminished MZ1851NN further down-regulated lesion. enhanced either culturing MZ1851LN at 26°C instead 37°C incubation both I-specific binding peptides, whereas not affected under these culture conditions. IFN-α particular IFN-γ treatment enhances steady-state and/or levels TAP, LMP, MZ1851 but had no additional effect on stability expression. These data indicate that malignant vivo selection tubular can lead recovery show stable an immune escape phenotype. Deficiencies phenotype involve all I-restricted presentation are least partially reversible IFN treatment, acquired potential.