Comparison of Antigen-Specific T-Cell Responses of Tuberculosis Patients using Complex or Single Antigens of Mycobacterium tuberculosis |
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| Authors: | MUSTAFA,AMOUDY,WIKER,ABAL,RAVN,OFTUNG,& ANDERSEN |
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| Affiliation: | ;Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait,;Institute of Immunology and Rheumatology, The National Hospital, Oslo, Norway,;Department of Medicine, Faculty of Medicine, Kuwait University and Chest Diseases Hospital, Ministry of Public Health, Kuwait,;Department of TB Immunology, Statens Serum Institut, Copenhagen, Denmark,;Department of Vaccinology, National Institute of Public Health, Oslo, Norway |
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| Abstract: | We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-γ (IFN-γ) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (rGroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis . The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M . tuberculosis , M . tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well as the vaccine strain, Mycobacterium bovis bacillus Calmette–Guérin (BCG). In addition, M . tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN-γ secretion showed that the most frequently recognized antigen was ESAT-6, followed by MPT59, GroES, MPB70, MPT64, DnaK, GroEL and PstS. The frequency of ESAT-6 responders, as measured both by proliferation (18/19) and secretion of IFN-γ (16/19) was comparable to the results obtained with whole-cell M . tuberculosis , MT-CF and M . bovis BCG. We also observed that most of the high responders to complex antigens recognized all of the antigens tested (covariation), demonstrating that the repertoire of human T-cell specificities induced by natural infection is directed towards several unrelated culture filtrate as well as somatic-derived protein antigens. In conclusion, the results obtained suggest that the cellular immune response in humans is directed against several important target antigens of M . tuberculosis and that some antigens, such as ESAT-6, are recognized by a high number of individuals. Such antigens represent candidates to be used for development of specific diagnostic reagents or in subunit vaccines. |
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