MUC-1 mucin made more immunogenic by presentation on dendritic cells

E. M. Hiltbold, P. Ciborowski, O. J. Finn

Research output: Contribution to journalArticlepeer-review

Abstract

The tumor antigen mucin (MUC-1) represents a unique target for immune-mediated attack of many breast and pancreatic tumors. MUC-1 which is normally expressed by epithelial cells as a highly polarized molecule becomes expressed over the entire surface of tumor cells where it becomes available for immune surveillance. A highly glycosylated protein, on normal cells, it is severly under-glycosylated on tumors, resulting in the exposure of new epitopes on the protein backbone. Though MUC-1 specific immune reponses have been demonstrated in patients with MUC-1+ tumors, these responses were not sufficient for elimination of tumor. Importantly, no MUC-1 specific helper T cell responses have been reported in patients to date. Our objective has been to discern how the T helper response to MUC-1 might best be initiated. We addressed this with a culture system in which in vitro-propagated dendritic cells were used to prime naive T cells. We tested the immunogenicity of several forms of the mucin protein in this system and examined the effect of various cytokines on the T cell responses. Strong mucin-specific CTL responses were generated when all forms of the protein were used to prime T cells. Our findings demonstrate however, that helper activity was strongest when T cells were primed to an unglycosylated peptide. T cells primed in the presence of IL-4 had a mixed phenotype with both helper and CTL activity, while those primed in IL-12 were almost exclusively cytolytic.

Original languageEnglish (US)
Pages (from-to)A888
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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