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 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 H2Kb and HLA-A*0201, and only to the mid-region for H2Db, 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.
Austin Research Institute, Heidelberg, Victoria, Australia.
V
V
Apostolopoulos
G
G
Chelvanayagam
P X
PX
Xing
I F
IF
McKenzie
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism* / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D017951:Antigen Presentation; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D002460:Cell Line; D003198:Computer Simulation; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006183:H-2 Antigens / Q000378:metabolism*; D006680:HLA Antigens / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000378:metabolism; D059848:HLA-DQ alpha-Chains; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic
D000906:Antibodies; D019138:Antibodies, Blocking; D006183:H-2 Antigens; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D015395:Histocompatibility Antigens Class I; D009077:Mucins; D010446:Peptide Fragments; D010047:Ovalbumin