Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line

We studied major histocompatibility complex (MHC) class I expression in 12 tumor cell culture lines established from patients with metastatic renal cell carcinoma (RCC). In one of these cell culture lines, UOK 123, we found no surface expression of β₂-microglobulin (β₂m) and MHC class I by flow cytometry. Immunofluorescence staining using three different monoclonal antibodies to p2m revealed no detectable β₂β₂endoplasmic reticulum (ER), Golgi apparatus, cytoplasm, or on the cell surface. There was no evidence of folded class I molecules inside or on the surface of the cells; however, the ER stained intensively for unfolded class I molecules. Transient expression of (32m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for β₂m resulted in normal expression of both β₂m and class I (HLA-A, B, C) determinants assessed by flow cytometry analysis. No expression of class I or β₂m was seen with the recombinant vaccinia vector carrying a control gene. The inability of class I molecules to reach the cell surface is due to the requirement of β₂m for proper folding and presentation of the class I MHC complex. The failure to assemble and express MHC class I complex on the cell surface renders these cells incapable of antigen presentation to cytotoxic T cells and provides a mechanism for escape from immune recognition by the tumor.