Impaired HLA-class-I stability in a sarcoma cell line which stimulates exclusively HLA-class-II-restricted autologous T cells
✍ Scribed by Michael Heike; Ute Schmitt; Alexandra Höhne; Christoph Huber; Karl-Hermann Meyer zum Büschenfelde; Barbara Seliger
- Book ID
- 102653649
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 678 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Defects in the generation and transport of antigenic peptides within tumor cells will lead to the expression of unstable HLA-class4 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-llrestricted autologous T-cell response against a human sarcoma cell line MZ-MES-I in vitro. Here, we show that surface HLAclass-I molecules of MZ-MES-I cells are unstable at physiological temperature. HLA-class4 surface expression of MZ-MES-I 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-l molecules by MZ-MES-I cells. Incubation with allele-specific HLA-class-I-binding peptides strongly increased HLA-class4 surface expression of MZ-MES-I sarcoma cells and TAP-deficient T2 cells in contrast to other tumor and B-cell lines tested in parallel. IFN--y enhanced the expression of TAP, LMP and HLA-class4 proteins in MZ-MES-I cells. However, the impaired stability of HLA-class4 surface molecules of MZ-MES-I could not be reversed by IFN-y. These results show a new example of impaired HLA-class4 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-ll-restricted T-cell responses against tumors with these defects.