Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ 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+ 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-gamma and had moderate cytolytic activity. We identified one core peptide sequence, PGSTAPPAHGVT, that elicits this response when it is presented by HLA-DR3.
Hiltbold
E M
EM
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Ciborowski
P
P
Finn
O J
OJ
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D020080:Tandem Repeat Sequences; D014407:Tumor Cells, Cultured
D016207:Cytokines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D018396:Mucin-1; D010446:Peptide Fragments