Modulation for antigen presentation in tuberculosis by using synthetic peptides.
Competition assay technology has been a very useful tool in the study of parasite antigens and has been inferred but never proven that this approach can be applied to select T-cell epitopes by using another microorganisms. In this study, HLA-restricted T-cell clones specific to synthetic peptides derived from the 65 kDa mycobacterial protein were used to investigate whether these peptides are able to compete with each other at the level of MHC-binding sites in tuberculosis. Fixed APCs were pulsed with suboptimal concentration of stimulator peptide in the presence of various concentrations of competitor peptide. The results showed that two peptides from this protein were able to compete with each other inducing a significant inhibition in the proliferation assays while there was no competition by using a control peptide. The amount of cross-reactivity was influenced by the peptide concentrations. More important was the observation that these peptides were able to bind to the same HLA-class II molecules therefore blocking the binding of each other. The fact that these peptides have not an identical amino acid sequence support the idea that the MHC-peptide interaction must have a broad specificity to be able to bind a large number of peptides. These results demonstrate that it is possible to modulate the antigen presentation by blocking the peptide MHC-class II interaction in tuberculosis and support the idea that this approach facilitates the selection of appropriate T-cell epitopes to be incorporated in a vaccine.
Méndez-Samperio
P
P
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, I.P.N., México, D.F., México.
Jiménez-Zamudio
L
L
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D018834:Chaperonin 60; D018833:Chaperonins; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D000939:Epitopes; D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins