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Naturally Processed Class II Epitope from the Tumor Antigen MUC1 Primes Human CD4⁺ T Cells¹

Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Epithelial cell mucin MUC1 is expressed on adenocarcinomas in an underglycosylated form that serves as a tumor antigen in breast, pancreatic, ovarian, and other tumors. Two predominant MUC1-specific immune responses are found in patients: CD8⁺ CTLs, which recognize tandemly repeated epitopes on the MUC1 protein core, and IgM antibodies. There have been no reports to date of MUC1-specific CD4⁺ T-helper cells in cancer patients. We show here that MUC1-specific CD4⁺ T cells are neither deleted nor tolerized and that CD4⁺ T cell responses can be generated when an appropriate soluble form of MUC1 is used. Naive CD4⁺ T cells from healthy donors were primed in vitro to a synthetic MUC1 peptide of 100 amino acids, representing five unglycosylated tandem repeats, presented by dendritic cells. They produced IFN- and had moderate cytolytic activity. We identified one core peptide sequence, PGSTAPPAHGVT, that elicits this response when it is presented by HLA-DR3.

¹ This work was supported by the Susan G. Komen Foundation Fellowship (to E. M. H.) and NIH Grants CA56103 (to O. J. F.) and CA73743 (to O. J. F. and P. C.).

² To whom requests for reprints should be addressed, at W1142 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. E-mail: ojfinn@vms.cis.pitt.edu.

Received 8/10/98. Accepted 9/28/98.

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