Open AccessCD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope
Author(s) -
Sarah A. Greaves,
Avinash Ravindran,
Radleigh G. Santos,
Lan Chen,
Michael T. Falta,
Yan Wang,
Angela M. Mitchell,
Shaikh M. Atif,
Douglas G. Mack,
Alex N. Tinega,
Lisa A. Maier,
Shaodong Dai,
Clemencia Pinilla,
Johan Grünewald,
Andrew P. Fontenot
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20210785
Subject(s) - elispot , aspergillus nidulans , epitope , immunology , antigen , microbiology and biotechnology , biology , antibody , sarcoidosis , medicine , pathology , genetics , cd8 , gene , mutant
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.