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

Heike, M; Schmitt, U; Höhne, A; Huber, C; Meyer zum Büschenfelde, KH

HERO ID

1090753

Reference Type

Journal Article

Year

1996

Language

English

PMID

8782668

HERO ID 1090753
In Press No
Year 1996
Title Impaired HLA-class-I stability in a sarcoma cell line which stimulates exclusively HLA-class-II-restricted autologous T cells
Authors Heike, M; Schmitt, U; Höhne, A; Huber, C; Meyer zum Büschenfelde, KH
Journal International Journal of Cancer
Volume 67
Issue 5
Page Numbers 743-748
Abstract 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.
Doi 10.1002/(SICI)1097-0215(19960904)67:5<743::AID-IJC25>3.0.CO;2-4
Pmid 8782668
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Is Qa No