Mycobacterial ESAT-6 and katG are recognized by sarcoidosis CD4+ T cells when presented by the American sarcoidosis susceptibility allele, DRB1*1101

J Clin Immunol. 2010 Jan;30(1):157-66. doi: 10.1007/s10875-009-9311-y. Epub 2009 Jun 18.

Abstract

Introduction: Genetic associations of American sarcoidosis susceptibility implicate MHC class II allele, DRB1*1101. We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD- healthy volunteers, and eight with latent tuberculosis infection.

Materials and methods: In order to further link these genetic and immunologic pillars of sarcoidosis pathogenesis, we performed flow cytometry on these same subjects to identify the cells responsible for immune responses to ESAT-6 and katG peptides, followed by HLA typing to determine allelic associations with recognition.

Discussion and conclusion: Sarcoidosis CD4+ T cells were primarily responsible for the systemic responses. Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP. Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101. ESAT-6 and katG presented by antigen-presenting cells expressing DRB1*1101-induced Th-1 responses from sarcoidosis T cells, thus providing a mechanistic insight for the association of HLA DRB1*1101 with sarcoidosis, and sarcoidosis T cell interaction with microbial antigens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Catalase / immunology
  • Catalase / metabolism*
  • Cell Separation
  • Cells, Cultured
  • Flow Cytometry
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism*
  • HLA-DRB1 Chains
  • Histocompatibility Testing
  • Host-Pathogen Interactions / genetics
  • Humans
  • Interferon-gamma / metabolism
  • Latent Tuberculosis / genetics*
  • Latent Tuberculosis / immunology*
  • Latent Tuberculosis / microbiology
  • Latent Tuberculosis / physiopathology
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Mycobacterium / immunology*
  • Mycobacterium / pathogenicity
  • Sarcoidosis, Pulmonary
  • United States

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 antigen, Mycobacterium leprae
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*11 antigen
  • Interferon-gamma
  • Catalase
  • katG protein, Mycobacterium tuberculosis