DIFFERENTIAL EXPRESSION OF MUC1 ON TRANSFECTED CELL-LINES INFLUENCES ITS RECOGNITION BY MUC1 SPECIFIC T-CELLS

In adenocarcinomas of the breast and pancreas, underglycosylation of t he glycoprotein MUC1, also expressed by normal breast and pancreatic d uctal epithelial cells, results in new protein epitopes to which the i mmune system mounts a cytotoxic T cell response. This cytotoxic immune response is directed primarily against epitopes on the tandem repeat domain of MUC1, and is unconventional in that it is major histocompati bility complex (MHC)-unrestricted. It is therefore necessary to invest igate the molecular basis of this immune response in order to enhance and optimize it for immune therapy purposes. In the present study, we characterize new MUC1 transfected human lymphoblastoid cell lines C1R and T2, and a pig kidney epithelial line LLC-PK1, that express MUC1 wi th either two repeats (MUC1-2R) or 22 repeats (MUC1-22R), and use them as stimulators and targets for cytotoxic T cells (CTL) in vitro. We s how that MUC1-2R is processed and glycosylated similarly to MUC1-22R. In contrast to MUC1-22R, MUC1-2R is not recognized by CTL on T2 and C1 R cells known for no or low MHC class I expression. It is however reco gnized when expressed at high density on xenogeneic LLC-PK1 cells. We propose that in MHC-unrestricted recognition, a large number of MUC1 e pitopes is necessary to effectively engage the T cell receptor, and th at in the presence of a low number of epitopes, engagement of the CD8 co-receptor by MHC class I molecules may be required for completing th e signal through the T cell receptor.