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

Identification of three non‐VNTR MUC1‐derived HLA‐A*0201‐restricted T‐cell epitopes that induce protective anti‐tumor immunity in HLA‐A2/Kb‐transgenic mice

“…The third peptide epitope (MUC 353-361 ) defined by Carmon et al 32 as being immunogenic in HLA-A2.1/D b -␤2-microglobulin single chain (HHD) transgenic mice was found by ourselves to be a weak binder to the HLA-A*0201 molecule and was not tested in the in vivo assays. Conversely the peptide MUC 264 -272 (FLSFHISNL) was found by Carmon et al 32 to be a weak binder to the hybrid HHD single chain molecule and was not analysed further by those investigators, whereas peptide MUC 79 -87 TLAPATEPA was not selected for testing. This again illustrates that different selection criteria and in vitro binding assays can result in the identification of distinct T-cell epitopes.…”

“…Peptide MUC [13][14][15][16][17][18][19][20][21] was also found to bind well to HLA-A*0201 in our experiments, but did not display immunogenicity in vivo (Table I). The third peptide epitope (MUC 353-361 ) defined by Carmon et al 32 as being immunogenic in HLA-A2.1/D b -␤2-microglobulin single chain (HHD) transgenic mice was found by ourselves to be a weak binder to the HLA-A*0201 molecule and was not tested in the in vivo assays. Conversely the peptide MUC 264 -272 (FLSFHISNL) was found by Carmon et al 32 to be a weak binder to the hybrid HHD single chain molecule and was not analysed further by those investigators, whereas peptide MUC 79 -87 TLAPATEPA was not selected for testing.…”

“…The report by Carmon et al 32 describes 3 MUC1-derived potential epitopes: MUC 13-21 (LLLTVLTVV), MUC 167-175 (ALASTAPPV) and MUC 353-361 (NLTISDVSV). As explained in Table III, one of these peptides (MUC 167-175 ) corresponds to one of the peptides we identified as being immunogenic and effective in tumour protection, although it differs by one amino acid from the sequence ALGSTAPPV defined in our experiments.…”

“…1 -2 The amino acid numbering used by Carmon et al 32 differs from our numbering. Since our MUC13-21 peptide matches the MUC32-40 peptide described by Carmon et al, 32 we conclude that their reference sequence must contain an additional 19 amino acids at the N-terminus.…”

“…Carmon et al 32 1 Our numbering is based on the MUC1 cDNA sequence including 2 tandem repeats as published by Gendler and co-workers. 1 -2 The amino acid numbering used by Carmon et al 32 differs from our numbering.…”