Immunity and tolerance to the tumor-associated antigen MUC1

摘要: Human mucin 1 (MUC1) is a highly glycosylated transmembrane glycoprotein that expressed on the luminal surface of ductal epithelial cells. adenocarcinomas overexpress MUC1 as tumor-associated antigen (TAA) presents to immune system peptide epitopes and glycopeptide with tumor specific carbohydrates, such mono- disaccharides known Tn, sialyl-Tn, TF antigens. Studies in transgenic (MUC1-Tg) mice have indicated that, compared transgene negative wild-type (WT) mice, MUC1-Tg maintains certain level tolerance peptide, reflected most notably decreased CD4 T cell help. We made novel observation contrast suppressed responses MUC1-peptide vaccine, vaccination resulted effective anti-MUC1 immunity similar elicited WT mice. hypothesized glycopeptides were seen foreign therefore not subject tolerance. To study we generated GST(GalNAc;Tn)A specific, MHC-Class II restricted hybridoma, RF6. cloned RF6 TCR (RFT; Va4.1Ja16-Vâ15Jâ1.3) RFT-Tg. Using RFT-Tg previously peptide-specific VFT-Tg show VFT cells transferred are through mechanisms peripheral tolerance, which induced against MUC1-glycopeptide RFT transiently activated upon transfer into suggesting epitope presented periphery healthy well bearing In contrast, thus treated antigens resulting activation glycopeptide-specific Simultaneous can break Our findings apply other TAA contain some "self" self ("foreign") affected by Understanding this distinction very important development safe cancer vaccines.