Premium
Identification of HLA‐A2‐restricted epitopes of the tumor‐associated antigen MUC2 recognized by human cytotoxic T cells
Author(s) -
Böhm Christian M.,
Hanski MarieLuise,
Stefanović Stefan,
Rammensee HansGeorg,
Stein Harald,
TaylorPapadimitriou Joyce,
Riecken ErnstOtto,
Hanski Christoph
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980302)75:5<688::aid-ijc5>3.0.co;2-v
Subject(s) - cytotoxic t cell , epitope , mucin , biology , antigen , pancreas , cancer research , human leukocyte antigen , ovarian cancer , microbiology and biotechnology , immunology , cancer , in vitro , biochemistry , genetics
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. Int. J. Cancer 75:688–693, 1998.© 1998 Wiley‐Liss, Inc.