NATURALLY PROCESSED CLASS-II EPITOPE FROM THE TUMOR-ANTIGEN MUC1 PRIMES HUMAN CD4(-CELLS() T)

Epithelial cell mucin MUC1 is expressed on adenocarcinomas in an under glycosylated form that serves as a tumor antigen in breast, pancreatic , ovarian, and other tumors. Two predominant MUC1-specific immune resp onses are found in patients: CD8(+) CTLs, which recognize tandemly rep eated epitopes on the MUC1 protein core, and IgM antibodies. There hav e been no reports to date of MUC1-specific CD4(+) T-helper cells in ca ncer patients. We show here that MUC1-specific CD4(+) T cells are neit her deleted nor tolerized and that CD4(+) T cell responses can be gene rated when an appropriate soluble form of MUC1 is used. Naive CD4(+) T cells from healthy donors were primed in vitro to a synthetic MUC1 pe ptide of 100 amino acids, representing five unglycosylated tandem repe ats, presented by dendritic cells. They produced IFN-gamma and had mod erate cytolytic activity. We identified one core peptide sequence, PGS TAPPAHGVT, that elicits this response when it is presented by HLA-DR3.