Naturally Processed Class II Epitope from the Tumor Antigen MUC1 Primes Human CD4 super(+) T Cells

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 super(+) CTLs, which recognize tandemly repeated epitopes...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-11, Vol.58 (22), p.5066-5070
Main Authors: Hiltbold, E M, Ciborowski, P, Finn, O J
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 super(+) 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 super(+) T-helper cells in cancer patients. We show here that MUC1-specific CD4 super(+) T cells are neither deleted nor tolerized and that CD4 super(+) T cell responses can be generated when an appropriate soluble form of MUC1 is used. Naive CD4 super(+) 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- gamma and had moderate cytolytic activity. We identified one core peptide sequence, PGSTAPPAHGVT, that elicits this response when it is presented by HLA-DR3.
ISSN:0008-5472