Immunization with f-Met peptides induces immune reactivity against Mycobacterium tuberculosis

Objective: To determine whether synthetic peptides containing an amino term inal formyl-methionine residue and corresponding to the sequence of several proteins produced by Mycobacterium tuberculosis, would elicit an immune re sponse in mice. Design: Peptides corresponding to the amino termini of 8 M. tuberculosis pr oteins and initiating with formyl methionine residues were synthesized. The ability of these peptides to bind to the mouse non-classical MHC class I m olecule H-2M3(a) was determined by flow microfluorimetry. These peptides we re used to pulse dendritic cells that were then injected into normal mice. These mice were subsequently challenged with aerosolized M. tuberculosis an d, 30 days later, the number of viable bacteria in the lungs was determined . Results: Four of the 8 synthetic peptides bound to H-2M3a and stabilized it s expression on the cell surface. Injection of mice with dendritic cells pu lsed with H-2M3(a) binding peptides elicited non-MHC restricted cytotoxic T lymphocytes that killed peptide pulsed target cells and macrophages infect ed with M. tuberculosis. Immunization of mice with syngeneic dendritic cell s pulsed in vitro with 2 of these peptides led to retardation of the growth of M, tuberculosis following aerosol challenge, Conclusion: Peptides that bind to non-polymorphic class I molecules can eli cit immune reactivity directed towards M. tuberculosis, (C) 2000 Harcourt P ublishers Ltd.