CELLULAR IMMUNE RECOGNITION OF HLA-A-ASTERISK-0201 FOLLOWING GENE-TRANSFER INTO A HUMAN EMBRYONAL CARCINOMA CELL-LINE

Previously, we have established that transcription and cell surface ex pression of MHC class I and beta(2)m genes in undifferentiated Tera-2 stem cells, a teratocarcinoma-derived cell line, was extremely low. In this study, we have transfected an HLA-A0201-encoding cDNA driven by the CMV-promoter into Tera-2 cells. Prior to IFN gamma treatment, mem brane expression of HLA-A0201 by these Tera-2 transfectants was nearl y lacking. Consequently, the HLA-A0201 Tera-2 transfectants were not recognized by the allo-HLA-A0201-specific CTL clone 3E7. Following IF N gamma treatment, which resulted in upregulation of HLA-A0201, Tera- 2 cells were lysed by CTL clone 3E7. In contrast, loading of HLA-A020 1 with the influenza-A-matrix peptide 58-66 resulted in partial lysis of Tera-2 cells by the influenza-A-matrix protein-specific CTL clone Q 66-9, and nearly complete lysis was observed following IFN gamma treat ment. These results suggest that the HLA-A0201 transgenes in Tera-2 c ells can be loaded with peptides and used as targets for peptide-speci fic CTLs.