6533b85efe1ef96bd12bfb95

RESEARCH PRODUCT

Impaired HLA-class-I stability in a sarcoma cell line which stimulates exclusively HLA-class-II-restricted autologous T cells

subject

description

Defects in the generation and transport of antigenic peptides within tumor cells will lead to the expression of unstable HLA-class-I molecules on the cell surface. These defects will allow tumor cells to escape an MHC-class-I-restricted T-cell response. Recently, we described an exclusively HLA-class-II-restricted autologous T-cell response against a human sarcoma cell line MZ-MES-1 in vitro. Here, we show that surface HLA-class-I molecules of MZ-MES-1 cells are unstable at physiological temperature. HLA-class-I surface expression of MZ-MES-1 cells could be strongly enhanced by culture at low temperature in contrast to various other cell lines analyzed in parallel. Furthermore, culture at low temperature decreased shedding of HLA-class-I molecules by MZ-MES-1 cells. Incubation with allele-specific HLA-class-I-binding peptides strongly increased HLA-class-I surface expression of MZ-MES-1 sarcoma cells and TAP-deficient T2 cells in contrast to other tumor and B-cell lines tested in parallel. IFN-gamma enhanced the expression of TAP, LMP and HLA-class-I proteins in MZ-MES-1 cells. However, the impaired stability of HLA-class-I surface molecules of MZ-MES-1 could not be reversed by IFN-gamma. These results show a new example of impaired HLA-class-I stability of a human tumor which coincides with lack of HLA-class-I-restricted autologous T cells recognizing this tumor. It underlines the importance of MHC-class-II-restricted T-cell responses against tumors with these defects.