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Anti-MUC1 Antibodies React Directly with MUC1 Peptides Presented by Class I H2 and HLA Molecules

Vasso Apostolopoulos^*, Gareth Chelvanayagam, Pei-Xiang Xing^* and Ian F. C. McKenzie^1,*

^* Austin Research Institute, Heidelberg, Victoria, Australia; and John Curtin School of Medical Research, Department of Human Genetics, Canberra, Australia

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 peptides that are bound within the groove of MHC class I molecules (H2 and HLA) 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-associated peptides but not to the N terminus were able to react with MUC1 peptides bound to H2K^b and HLA-A*0201, and only to the mid-region for H2D^b, by flow cytometry and also to block CTL activity. Molecular modeling showed that the N terminus is buried (and not accessible), whereas the midpeptide residues form a loop and the C terminus is free, making 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.

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