Cell-Mediated Immune Responses to Complex and Single Mycobacterial Antigens in Tuberculosis Patients with Diabetes

Mustafa, Abu Salim; El-Shamy, Abdulsalam M.; Madi, Nada; Amoudy, Hanady A.; Al‐Attiyah, Rajaa

doi:10.1159/000129614

Cited by 14 publications

(19 citation statements)

References 40 publications

(33 reference statements)

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“…The overall results suggest that infection with M. tuberculosis did not affect the level of Th1 cell reactivity to BCG and most antigens of M. tuberculosis used in this study. Furthermore, the study confirms strong to moderate (10,50). Although the gene for PPE68 is present in the M. tuberculosis-specific RD1 segment (13,36), statistically similar responses in the ESAT-6/CFP10 responders and nonresponders could be due to the presence of an immunodominant epitope (aa 124 to 137), which is conserved in several PPE proteins of M. tuberculosis, BCG, and environmental mycobacteria (48,57).…”

Section: Discussionsupporting

confidence: 54%

“…The complex mycobacterial antigens used in this study were irradiated whole-cell M. tuberculosis H37Ra and M. bovis BCG (29,50), M. tuberculosis culture filtrate (MT-CF) enriched for secreted antigens, and purified M. tuberculosis cell walls (MT-CW) (48). MT-CF and MT-CW were kindly provided by J. T. Belisle (Colorado State University, Fort Collins, CO).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Evaluation of MPT83 (Rv2873) for T Helper-1 Cell Reactivity and Identification of HLA-Promiscuous Peptides in Mycobacterium bovis BCG-Vaccinated Healthy Subjects

Mustafa

2011

Clin Vaccine Immunol

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Section: Discussionsupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Comparative Evaluation of MPT83 (Rv2873) for T Helper-1 Cell Reactivity and Identification of HLA-Promiscuous Peptides in Mycobacterium bovis BCG-Vaccinated Healthy Subjects

Mustafa

2011

Clin Vaccine Immunol

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“…A number of studies performed in the past have shown that MPT64 is relevant to immune response in humans [2][3][4][5] , and immunization of experimental animals with preparations containing MPT64 provided protection against challenge with M. tuberculosis [6] . Although these studies encourage the use of MPT64 as a new candidate vaccine against TB, this protein requires further characterization for promiscuous recognition by the immune system of M. tuberculosis -infected healthy individuals who did not progress to active disease, most probably due to the development of protective immunity.…”

Section: Introductionmentioning

confidence: 99%

Mapping of Th1-Cell Epitope Regions of Mycobacterium tuberculosis Protein MPT64 (Rv1980c) Using Synthetic Peptides and T-Cell Lines from M. tuberculosis-Infected Healthy Humans

Mustafa

Shaban

2010

Med Princ Pract

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Objective: To identify T helper 1 (Th1)-cell stimulating and HLA-promiscuous peptides of MPT64 (Rv1980c), a major secreted antigen of Mycobacterium tuberculosis. Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 35 healthy subjects and typed for HLA-DR molecules using genomic methods. To identify subjects infected with M. tuberculosis, PBMCs were tested in antigen-induced proliferation assays with whole cells and culture filtrate antigens of M. tuberculosis, M. tuberculosis-specific antigens ESAT-6 and CFP10, and MPT64. Culture filtrate-induced T-cell lines were established in vitro from 12 M. tuberculosis-infected and HLA-heterogeneous healthy subjects, and tested with 20 overlapping synthetic peptides covering the sequence of MPT64 in Th1-cell assays, i.e. antigen-induced proliferation and/or IFN-γ secretion. In addition, T-cell lines from three HLA-heterogeneous subjects were tested for cytotoxic activity against peptide-pulsed antigen-presenting cells. Results: PBMCs from 12 of 35 subjects responded to M. tuberculosis-specific antigens ESAT-6 and CFP10 as well as to MPT64, which suggested that they were infected with M. tuberculosis. Ten of twelve T-cell lines established from these donors responded to MPT64, and nine T-cell lines responded to 1 or more of the peptides of MPT64 in anti- gen-induced proliferation assays. Furthermore, 18 of the 20 peptides of MPT64 were recognized by the T-cell lines in 1 or more assay systems, and at least 5 peptides were recognized by T-cell lines from HLA-DR-heterogeneous subjects. Conclusion: Th1-cell-reactive epitopes are scattered throughout the sequence of MPT64, and at least 5 of its peptides are presented to Th1-cells in a HLA-promiscuous manner.

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“…Previous studies have shown that MPT64 is recognized by TB patients in immunological assays [7][8][9][10][11] . In addition, MPT64 has also been shown to protect against M. tuberculosis infection in mouse models of TB [12,13] .…”

Section: Introductionmentioning

confidence: 99%

HLA-Promiscuous Th1-Cell Reactivity of MPT64 (Rv1980c), a Major Secreted Antigen of Mycobacterium tuberculosis, in Healthy Subjects

Mustafa

2009

Med Princ Pract

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Objective: To determine HLA-promiscuous Th1-cell reactivity of MPT64 (Rv1980c) in healthy humans. Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy subjects (n = 61) and HLA typed genomically. PBMCs were tested for Th1-cell reactivity (antigen-induced proliferation and interferon-γ secretion) with complex antigens (whole cells, culture filtrate and cell walls) and single secreted antigens (Ag85B, MPT64 and MPB70) of Mycobacterium tuberculosis. In addition, culture-filtrate-induced T-cell lines were established from PBMCs of 14 donors and tested with the above antigens in Th1-cell assays. Furthermore, 3 T-cell lines were tested for cytotoxic activity against MPT64-pulsed monocytes/macrophages, and a T-cell line was analysed for HLA restriction in antigen presentation using anti-HLA class I and class II monoclonal antibodies and HLA-DR-typed antigen-presenting cells. Results: PBMCs showed strong Th1-cell reactivity with all of the complex mycobacterial antigens, whereas MPT64 induced moderate Th1-cell reactivity, which was comparable to the reactivity induced by other previously characterized secreted antigens of M. tuberculosis, i.e. Ag85B and MBP70. Furthermore, HLA heterogeneity of the responding donors suggested that MPT64 was presented to Th1 cells promiscuously. Testing of the T-cell lines confirmed that Th1 cells contributed to the promiscuous antigen-specific reactivity observed with PBMCs and exhibited cytotoxic activity against MPT64-pulsed monocytes/macrophages. In addition, a T-cell line investigated for HLA restriction analysis showed that MPT64 was presented to T cells in association with HLA-DR molecules in a promiscuous manner. Conclusion: MPT64 is promiscuously recognized by human Th1 cells with cytotoxic activity and therefore deserves consideration as a candidate vaccine against tuberculosis in humans.

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Cell-Mediated Immune Responses to Complex and Single Mycobacterial Antigens in Tuberculosis Patients with Diabetes

Cited by 14 publications

References 40 publications

Comparative Evaluation of MPT83 (Rv2873) for T Helper-1 Cell Reactivity and Identification of HLA-Promiscuous Peptides in Mycobacterium bovis BCG-Vaccinated Healthy Subjects

Comparative Evaluation of MPT83 (Rv2873) for T Helper-1 Cell Reactivity and Identification of HLA-Promiscuous Peptides in Mycobacterium bovis BCG-Vaccinated Healthy Subjects

Mapping of Th1-Cell Epitope Regions of <i>Mycobacterium tuberculosis</i> Protein MPT64 (Rv1980c) Using Synthetic Peptides and T-Cell Lines from <i>M. tuberculosis</i>-Infected Healthy Humans

HLA-Promiscuous Th1-Cell Reactivity of MPT64 (Rv1980c), a Major Secreted Antigen of <i>Mycobacterium tuberculosis</i>, in Healthy Subjects

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