ANTI-MUC1 ANTIBODIES REACT DIRECTLY WITH MUC1 PEPTIDES PRESENTED BY CLASS-I H2 AND HLA MOLECULES

Peptides bound in the groove of MHC class I molecules and detected by CTLs are not normally accessible to Ab, We now report that MUC1 peptid es that are bound within the groove of MHC class I molecules (H2 and H LA) and that can be detected by CTLs can also be detected by anti-MUC1 Abs, mAbs to the middle and C-terminal regions of the class I-associa ted peptides but not to the N terminus were able to react with MUC1 pe ptides bound to H2K(b) and HLA-A0201, and only to the mid-region for H2D(b), by flow cytometry and also to block CTL activity. Molecular mo deling showed that the N terminus is buried (and not accessible), wher eas the midpeptide residues form a loop and the C terminus is free, ma king these two regions accessible to Ab. The findings demonstrate for the first time that peptides associated with class I molecules can be detected by anti-peptide Abs.