Identification of HLA-A2-restricted epitopes of the tumor-associated antigen MUC2 recognized by human cytotoxic T cells

Abstract

Previous studies have shown that self-antigens overexpressed in malignant tissue can provide a basis for a tumor-specific immune response. The mucin MUC2 is strongly overexpressed in all mucinous tumors of colon, breast, ovary and pancreas. In the corresponding normal tissue it is either not expressed (breast, ovary, pancreas) or it is expressed at considerably lower levels than in the mucinous tumors (colon). We therefore investigated whether the MUC2 molecule comprises HLA-A2-binding epitopes recognized by human cytotoxic T cells. Four MUC2 peptides with high affinity and stable binding to HLA-A2 were identified. Those peptides and additionally 3 peptides with moderate binding to HLA-A2 were loaded onto dendritic cells, which were used for stimulation of autologous T cells from healthy donors. Two MUC2 peptides, which belonged to the group of stable binders, induced specific cytotoxic T-cell lines. Target cells loaded with these peptides were strongly lysed in a concentration-dependent and HLA-A2-restricted manner. Our data show that the tumor-associated mucin MUC2 has potential as a target antigen for cytotoxic T cells in patients with mucinous carcinomas.