T-Cell Antigens of Mycobacterium immunogenum, an Etiological Agent of Occupational Hypersensitivity Pneumonitis

Details

• Personal Author:
  Chandra H ; Yadav JS
• Description:
  The T lymphocyte-mediated immune lung disease hypersensitivity pneumonitis (HP) in machinists is poorly understood for disease mechanisms and diagnosis due in part to lack of information on causative T-cell antigens of the etiological agent Mycobacterium immunogenum (MI). Therefore, overall objective of the current study was to identify T-cell reactive antigens of this recently recognized pathogen. In this direction, purified recombinant form of five of the seroreactive proteins (reported in our initial study), including three cell wall-associated (arbitrarily designated as antigens A through C) and two secretory (AgD & AgE), were examined for their potential to activate antigen-presenting cells (APCs) viz. alveolar macrophages and human monocyte-derived dendritic cells (DCs) and for T-cell reactivity. All five proteins strongly activated APCs by inducing inflammatory cytokines (TNF-a, IL-6 & IL-1a) and nitric oxide (NO), albeit to a varying extent (AgE >/= AgD > AgB >/= AgA >/= AgC), implying their differential potential for activation of APCs. However, only two of the five proteins (AgA, AgD) showed significant T-cell response (T lymphocyte proliferation and IFN-gamma secretion) when tested using sensitized T-cells from MI-induced HP mouse model. These antigens also activated the human naïve CD4+ T cells in presence of autologous DCs as measured using ELISPOT for IFN-gamma. Immuno-informatic analysis predicted that the identified T-cell antigens (AgA and AgD) bind more number of class I and class II HLA alleles as compared with the reference immuno-dominant antigens ESAT-6 and CFP-10 from the tuberculous mycobacterial species M. tuberculosis. Predicted human population coverage for the epitopes of AgA (90.87%) and AgD (88.09%) was also higher as compared to those for the reference antigens ESAT-6 (82.42%) and CFP-10 (80.21%). These two antigens were further predicted to be highly immunogenic for class I peptide MHC (pMHC) complex as compared to the reference antigens. Collectively, our results imply that AgA and AgD are T-cell antigens with a high HLA binding frequency as well as population coverage for HLA alleles. This first report on T-cell antigens and epitopes of M. immunogenum is significant as it is expected to open up avenues for understanding pathogenesis mechanisms and developing T-cell-based immunodiagnostic tools for this poorly investigated occupational lung disease. [Description provided by NIOSH]
• Subjects:
  Animals Antigens Immune System Inhalation Exposure Lung Diseases Manufacturing And Industrial Facilities Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Author Keywords: Mycobacterium Immunogenum Epitopes HLA Alleles Hypersensitivity Pneumonitis IFN-gamma Response Immune Reaction Inhalants Lung Disease Machine Operators Metalworking Fluids MWFs Mycobacterium T Cell Antigens

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• ISSN:
  0161-5890
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  168-177
• Volume:
  75
• NIOSHTIC Number:
  nn:20052371
• Citation:
  Mol Immunol 2016 Jul; 75:168-177
• Contact Point Address:
  Jagjit S. Yadav, Microbial Pathogenesis and Toxicogenomics Laboratory, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056
• Email:
  jagjit.yadav@uc.edu
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Molecular Immunology
• End Date:
  20170731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1e6b89e3a9cf7285c289ef08a33e4de8b65140224a1ed0f84ee18a9912dcc1855c57936f481bb3672c7cd0449e9fcfe9f8f8d295390fe338405a698f71732566
• Download URL:
  https://stacks.cdc.gov/view/cdc/211907/cdc_211907_DS1.pdf
• File Type:
  [PDF - 2.09 MB ]