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

J Exp Med. 2021 Oct 4;218(10):e20210785. doi: 10.1084/jem.20210785. Epub 2021 Aug 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, Fungal / immunology
  • Aspergillus nidulans / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / microbiology*
  • Case-Control Studies
  • 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
  • Sarcoidosis / immunology*


  • Antigens, Fungal
  • Epitopes, T-Lymphocyte
  • Fungal Proteins
  • HLA-DR3 Antigen
  • Immunoglobulin G