Mechanisms of escape from CD8+ T‐cell clones specific for the HER‐2/NEU proto‐oncogene expressed in ovarian carcinomas: Related and unrelated to decreased MHC class 1 expression

1clones. Cell surface expression of HLA A2 was markedly decreased on all 3 escape variants, relative to the parental tumor line, while no significant decrease in their expression of the HER-2/neu, ICAM-1 or LFA-3 molecules was found. There was a correlation between the level of tumor-specific recognition and HLA A2 expression among the tumor clones isolated from 2 of the escape variants (EVC8 and EVC36). In contrast, high HLA A2-expressing tumor clones isolated from the EVC22 variant, or EVC22 which had regained high HLA A2 expression through IFN-g treatment, were not recognized by the HER-2/neu-specific TCD8 1 clone C-22. No mutations were found in the cDNA or the genomic DNA derived from the PCR product corresponding to a 496 bp fragment including the region coding for the E75 epitope of the HER2/neu gene in the EVC22 variant. Collectively, this in vitro model underlines the importance of decreased expression of the HLA restriction element for escape from tumor-specific TCD8 1