title: Comparative evaluation of MPT83 (Rv2873) for T helper-1 cell reactivity and identification of HLA-promiscuous peptides in Mycobacterium bovis BCG-vaccinated healthy subjects.
abstract: MPT83 (Rv2873), a surface lipoprotein excreted in the culture of Mycobacterium tuberculosis, is immunoreactive in antibody assays in humans and animals and provides protection as a combined DNA vaccine in mice and cattle. This study was undertaken to determine the reactivity of MPT83 in T helper 1 (Th1)-cell assays, i.e., antigen-induced proliferation and gamma interferon (IFN-γ) secretion, using peripheral blood mononuclear cells (PBMCs) obtained from Mycobacterium bovis bacillus Calmette-Guérin (BCG)-vaccinated and/or M. tuberculosis-infected healthy subjects. PBMCs were tested with complex mycobacterial antigens and pools of synthetic peptides corresponding to MPT63, MPT83, MPB70, LppX, PPE68, CFP10, and ESAT-6. The results showed that MPT83 is among the strongest Th1 cell antigens of M. tuberculosis, and it was recognized equally strongly by BCG-vaccinated and by BCG-vaccinated and M. tuberculosis-infected healthy subjects. Furthermore, HLA heterogeneity of the responding donors suggested that MPT83 was presented to Th1 cells by several HLA-DR molecules. The analysis of the mature MPT83 sequence (amino acids [aa] 1 to 220) and its 14 overlapping synthetic peptides for binding prediction to HLA class II molecules and actual recognition of the peptides by PBMCs from HLA-DR-typed subjects in antigen-induced proliferation and IFN-γ assays suggested that Th1 cell epitopes were scattered throughout the sequence of MPT83. In addition, the HLA-promiscuous nature of at least three peptides, i.e., P11 (aa 151 to 175), P12 (aa 166 to 190), and P14 (aa 196 to 220), was suggested by HLA-DR binding predictions and recognition by HLA-DR heterogeneous donors in Th1 cell assays. These results support the inclusion of MPT83 in an antigen cocktail to develop a new antituberculosis vaccine.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait. abusalim@hsc.edu.kw
authors.forename: Abu S
authors.initials: AS
authors.lastname: Mustafa
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology*; D011485:Protein Binding; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D006684:HLA-DR Antigens; C094904:MPB83 protein, Mycobacterium; D008565:Membrane Proteins; D007371:Interferon-gamma