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.
CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope
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.
- Award Id(s): HL136137,HL102245,HL62410,ES02534
- Award Id(s): 20190478
- Award Id(s): 2019-01034
- Award Id(s): 20180120
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Sarah A. Greaves, Avinash Ravindran, Radleigh G. Santos, Lan Chen, Michael T. Falta, Yang Wang, Angela M. Mitchell, Shaikh M. Atif, Douglas G. Mack, Alex N. Tinega, Lisa A. Maier, Shaodong Dai, Clemencia Pinilla, Johan Grunewald, Andrew P. Fontenot; CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope. J Exp Med 4 October 2021; 218 (10): e20210785. doi: https://doi.org/10.1084/jem.20210785
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