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.

中文翻译：

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急性结节病患者肺部的 CD4 + T 细胞识别构巢曲霉表位

Löfgren 综合征 (LS) 是一种急性形式的结节病，其特征是与HLA-DRB1*03 (HLA-DR3) 遗传相关，并且在支气管肺泡灌洗液 (BAL) 中积累了未知特异性的 CD4 ^{+ T 细胞。}在这里，我们筛选了相关的 LS 特异性 TCR 的抗原特异性，并鉴定了一种源自构巢曲霉的 NAD 依赖性组蛋白脱乙酰酶 hst4 (NDPD) 的肽，它以 HLA-DR3 限制的方式刺激这些 CD4 ^{+ T 细胞。使用 ELISPOT 分析，与 DR3 +}相比，DR3 ⁺ LS 受试者的 BAL 中更多数量的 IFN-γ 和 IL-2 分泌 T 细胞观察到对照受试者对NDPD肽的反应。^{最后，在 DR3 +} LS 受试者的血清中检测到对构巢曲霉NDPD 的IgG 抗体反应增加。因此，我们的研究结果确定了源自 LS 患者肺部的CD4 ^{+ T 细胞的配体，并表明}构巢曲霉在 LS 病因学中的作用。