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

Oswald-Richter K, Sato H, Hajizadeh R, Shepherd BE, Sidney J, Sette A, Newman LS, Drake WP
J Clin Immunol. 2010 30 (1): 157-66

PMID: 19536643 · PMCID: PMC2821522 · DOI:10.1007/s10875-009-9311-y

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.

MeSH Terms (23)

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

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