Naturally Processed Class II Epitope from the Tumor Antigen

Epithelial cell mucin Ml (I is expressed on adenocarcinomas in an underglycosylated form that serves as a tumor antigen in breast, pancre atic, ovarian, and other tumors. Two predominant MUC1-specific im mune responses arc found in patients: CDS* CTLs, which recognize tandemly repeated epitopes on the Miri protein core, and IgM antibod ies. There have been no reports to date of MUCl-specific CD4* T-helper cells in cancer patients. We show here that MUCl-specific CD4+ T cells are neither deleted nor tolerized and that ( 1)4 ' T cell responses can be generated when an appropriate soluble form of Ml (I is used. Naive ( 1)4 ' T cells from healthy donors were primed in vitro to a synthetic MICI peplide of 100 amino acids, representing five unglycosylated tan dem repeats, presented by dendritic cells. They produced II-N-y and had moderate cytolytic activity. We identified one core peptide sequence, PGSTAPPAHGVT. that elicits this response when it is presented by HLA-DR3.