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


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.


CONCLUSIONS
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.
Oswald-Richter
Kyra
K
Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, USA.
Sato
Hiroe
H
Hajizadeh
Rana
R
Shepherd
Bryan E
BE
Sidney
John
J
Sette
Alessandro
A
Newman
Lee S
LS
Drake
Wonder Puryear
WP
D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002374:Catalase / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D055985:Latent Tuberculosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000276:immunology* / Q000472:pathogenicity; D017565:Sarcoidosis, Pulmonary; D014481:United States
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C525005:ESAT-6 antigen, Mycobacterium leprae; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C508422:HLA-DRB1*11 antigen; D007371:Interferon-gamma; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis