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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. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, USA.

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.

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CD4+ T cell responses are partially blocked by anti-HLA-DR and anti-HLA-DQ antibodies. Consistent with independent reports from other labs, immune responses to ESAT-6 and katG were blocked with monoclonal antibody against HLA-DR. Partial inhibition of immune recognition also was observed with monoclonal antibody against HLA-DQ. HLA-DP did not appear to have a role in ESAT-6 antigen presentation
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Fig2: CD4+ T cell responses are partially blocked by anti-HLA-DR and anti-HLA-DQ antibodies. Consistent with independent reports from other labs, immune responses to ESAT-6 and katG were blocked with monoclonal antibody against HLA-DR. Partial inhibition of immune recognition also was observed with monoclonal antibody against HLA-DQ. HLA-DP did not appear to have a role in ESAT-6 antigen presentation

Mentions: HLA-DR and HLA-DQ Inhibits Recognition of Mycobacterial Peptides After the observance of mainly CD4+ T cell responses to mycobacterial peptides, we investigated for HLA class II restriction of immune recognition of ESAT-peptide. Using flow cytometry, we examined the effects of mAbs against HLA-DR, -DQ, and -DP on antigen presentation of ESAT-6 and katG (Fig. 2). Immune recognition of ESAT-6 peptide was partially inhibited after blocking antigen presentation with anti-HLA-DR or anti-HLA-DQ mAb. Monoclonal antibody against HLA-DP had no effect.Fig. 2


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. (2009)

CD4+ T cell responses are partially blocked by anti-HLA-DR and anti-HLA-DQ antibodies. Consistent with independent reports from other labs, immune responses to ESAT-6 and katG were blocked with monoclonal antibody against HLA-DR. Partial inhibition of immune recognition also was observed with monoclonal antibody against HLA-DQ. HLA-DP did not appear to have a role in ESAT-6 antigen presentation
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821522&req=5

Fig2: CD4+ T cell responses are partially blocked by anti-HLA-DR and anti-HLA-DQ antibodies. Consistent with independent reports from other labs, immune responses to ESAT-6 and katG were blocked with monoclonal antibody against HLA-DR. Partial inhibition of immune recognition also was observed with monoclonal antibody against HLA-DQ. HLA-DP did not appear to have a role in ESAT-6 antigen presentation
Mentions: HLA-DR and HLA-DQ Inhibits Recognition of Mycobacterial Peptides After the observance of mainly CD4+ T cell responses to mycobacterial peptides, we investigated for HLA class II restriction of immune recognition of ESAT-peptide. Using flow cytometry, we examined the effects of mAbs against HLA-DR, -DQ, and -DP on antigen presentation of ESAT-6 and katG (Fig. 2). Immune recognition of ESAT-6 peptide was partially inhibited after blocking antigen presentation with anti-HLA-DR or anti-HLA-DQ mAb. Monoclonal antibody against HLA-DP had no effect.Fig. 2

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, USA.

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.

Show MeSH
Related in: MedlinePlus