Novel breast-tumor-associated MUC1-derived peptides: Characterization in Db−/− × β2 microglobulin (β2m) null mice transgenic for a chimeric HLA-A2.1/Db-β2 microglobulin single chain
✍ Scribed by Lior Carmon; Khaled M. el-Shami; Adrian Paz; Steve Pascolo; Esther Tzehoval; Boaz Tirosh; Romelin Koren; Michael Feldman; Mati Fridkin; François A. Lemonnier; Lea Eisenbach
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- French
- Weight
- 170 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The MUC1 protein was found to be up-regulated in a spectrum of malignant tumors. T-cell responses to the MUC1 extracellular tandem repeat array (TRA) were observed in murine models as well as in breast-carcinoma patients. In the present study, we evaluated the anti-tumor potential of HLA-A2.1-motif-selected peptides from non-TRA domains of the molecule. Peptide immunogenicity was examined in the D b؊ / ؊ ؋ 2 microglobulin (2m) null mice transgenic for a modified HLA-A2.1/D b -2 microglobulin single chain (HHD mice). Our results show the existence of 3 novel HLA-A2.1restricted MUC1-derived cytotoxic T-lymphocyte (CTL) epitopes. These peptides are processed and presented by the HHD-transfected breast-tumor cell line MDA-MB-157. Moreover, CTL induced by these 3 peptides show higher lysis of target cells pulsed with breast-carcinoma-derived peptides than of targets pulsed with normal breast-tissue-derived peptides. These data suggest an important role for non-TRA MUC1-derived peptides as inducers of a MHC-restricted CTL reaction to a breast-carcinoma cell line and patient-derived tumor extracts.