Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken up by dendritic cells

We previously reported that the glycosylated MUC1 tumor antigen circulating as soluble protein in patients' serum is not processed by dendritic cells and does not elicit MHC-Class II-restricted T helper responses in vitro. In contrast, a long synthetic peptide from the MUC1 tandem repeat region is p resented by Class II molecules, resulting in the initiation of T helper cel l responses. Here we addressed the ability of dendritic cells to present va rious glycosylated or not glycosylated forms of MUC1 by MHC Class I. We fou nd that three different forms of MUC1, ranging from glycosylated and underg lycosylated protein to unglycosylated synthetic peptide, were able to elici t MUC1-specific, Class-I-restricted CTL responses. The efficiency of proces sing and the resulting strength of CTL activity were inversely correlated w ith the degree of glycosylation of the antigen. Furthermore, the more effic iently processed 100mer peptide primed a broader repertoire of CTL than the glycosylated protein. (C) 1999 Academic Press.