CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope

Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified...

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Published inThe Journal of experimental medicine Vol. 218; no. 10
Main Authors Greaves, Sarah A., Ravindran, Avinash, Santos, Radleigh G., Chen, Lan, Falta, Michael T., Wang, Yang, Mitchell, Angela M., Atif, Shaikh M., Mack, Douglas G., Tinega, Alex N., Maier, Lisa A., Dai, Shaodong, Pinilla, Clemencia, Grunewald, Johan, Fontenot, Andrew P.
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 04.10.2021
Subjects
Adult
Animals
Antigens, Fungal - immunology
Aspergillus nidulans - immunology
Case-Control Studies
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - microbiology
Epitopes, T-Lymphocyte - immunology
Female
Fungal Proteins - immunology
HLA-DR3 Antigen - chemistry
HLA-DR3 Antigen - genetics
HLA-DR3 Antigen - immunology
Humans
Hybridomas - immunology
Immunoglobulin G
Male
Mice, Transgenic
Middle Aged
Mucosal Immunology
Sarcoidosis - immunology
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Abstract Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.
AbstractList Löfgren's syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3-restricted manner. Using ELISPOT analysis, a greater number of IFN-γ- and IL-2-secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.Löfgren's syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3-restricted manner. Using ELISPOT analysis, a greater number of IFN-γ- and IL-2-secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.
Löfgren's syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3-restricted manner. Using ELISPOT analysis, a greater number of IFN-γ- and IL-2-secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.
We identify a peptide derived from Aspergillus nidulans recognized by CD4 + T cells derived from the lungs of Löfgren’s syndrome (LS) patients and provide evidence that A. nidulans plays a role in the pathogenesis of LS. Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4 + T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4 + T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3 + LS subjects compared with DR3 + control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3 + LS subjects. Thus, our findings identify a ligand for CD4 + T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.
Author Tinega, Alex N.
Grunewald, Johan
Mack, Douglas G.
Greaves, Sarah A.
Mitchell, Angela M.
Wang, Yang
Pinilla, Clemencia
Dai, Shaodong
Ravindran, Avinash
Fontenot, Andrew P.
Santos, Radleigh G.
Maier, Lisa A.
Falta, Michael T.
Atif, Shaikh M.
Chen, Lan
AuthorAffiliation 4 Department of Mathematics, Nova Southeastern University, Ft. Lauderdale, FL
5 Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO
6 Department of Medicine, National Jewish Health, Denver, CO
7 Center for Translational Science, Florida International University, Port St. Lucie, FL
1 Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
3 Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
8 Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO
2 Department of Medicine, Solna, Karolinska University Hospital, Stockholm, Sweden
AuthorAffiliation_xml – name: 5 Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO
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– name: 1 Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
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– name: 8 Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO
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J. Grunewald and A.P. Fontenot contributed equally to this paper.
Disclosures: L.A. Maier reported grants from NIH (1R01HL114587-01A1; 1R01 HL140357-01A1; R01HL136681-01A1; 1R01 HL142049-01A1; R01 HL127461), FSR, Clinical Studies Network, and MNK14344100 outside the submitted work; in addition, L.A. Maier is a member of the FSR Scientific Advisory Board. She does not receive any compensation for this activity. No other disclosures were reported.
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– reference: 34515726 - J Exp Med. 2021 Oct 4;218(10):
SSID ssj0014456
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Snippet Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells...
Löfgren's syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells...
We identify a peptide derived from Aspergillus nidulans recognized by CD4 + T cells derived from the lungs of Löfgren’s syndrome (LS) patients and provide...
SourceID swepub
pubmedcentral
proquest
pubmed
crossref
SourceType Open Access Repository
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Enrichment Source
SubjectTerms Adult
Animals
Antigens, Fungal - immunology
Aspergillus nidulans - immunology
Case-Control Studies
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - microbiology
Epitopes, T-Lymphocyte - immunology
Female
Fungal Proteins - immunology
HLA-DR3 Antigen - chemistry
HLA-DR3 Antigen - genetics
HLA-DR3 Antigen - immunology
Humans
Hybridomas - immunology
Immunoglobulin G
Male
Mice, Transgenic
Middle Aged
Mucosal Immunology
Sarcoidosis - immunology
Title CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope
URI https://www.ncbi.nlm.nih.gov/pubmed/34410304
https://www.proquest.com/docview/2562830925
https://pubmed.ncbi.nlm.nih.gov/PMC8383815
http://kipublications.ki.se/Default.aspx?queryparsed=id:147695604
Volume 218
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