Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren's Syndrome.
Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren's Syndrome.
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DOI：
10.4049/jimmunol.1700570
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发表时间：
2017-10-01
期刊：
影响因子：
--
通讯作者：
Fontenot AP
中科院分区：
文献类型：
--
作者：
Mitchell AM;Kaiser Y;Falta MT;Munson DJ;Landry LG;Eklund A;Nakayama M;Slansky JE;Grunewald J;Fontenot AP
结节病是一种主要影响肺部的肉芽肿性疾病，其特征是在支气管肺泡灌洗液(BAL)中聚集了CD4+T细胞。先前的研究表明，人类白细胞抗原-DRB1*03：01+(DR3+)患者被诊断为该疾病的急性形式，L综合征(LS)，有积聚的CD4+T细胞利用TRAV12-1(以前的AV2S3)携带TCR。然而，这些α链在疾病发病机制中的重要性以及成对的β链仍不清楚。本研究旨在鉴定αβ+LS患者外周血中CD4+T细胞表达的扩增的DR3TCR对。使用深度测序方法，我们确定了LS患者BALα+T细胞上表达的TCRβ和TCR TCR链以及αβTCR对。TRAV12-1和TRBV2(原BV22)是DR3+LS患者V区扩增最多的基因片段，多个DR3+LS患者共享TRAV12-1和TRBV2 CDR3基序。TRAV12-1与αβTCR配对时，TRAV12-1优先与TRBV2配对，这些TRAV12-1/TRBV2TCR显示CDR3同源性。这些发现表明，L综合征患者中存在公共的CD_4~+T细胞受体谱系，这些T细胞正在识别人类白细胞抗原-DR3中可能的结节病相关抗原(S)。
Sarcoidosis is a granulomatous disease that primarily affects the lungs and is characterized by an accumulation of CD4+ T cells in the bronchoalveolar lavage (BAL). Previous work has indicated that HLA-DRB1*03:01+ (DR3+) patients diagnosed with the acute form of the disease, Löfgren’s syndrome (LS), have an accumulation of CD4+ T cells bearing TCRs utilizing TRAV12-1 (formerly AV2S3). However, the importance of these α-chains in disease pathogenesis and the paired TCRβ chain remains unknown. This study aimed to identify expanded αβTCR pairs expressed on CD4+ T cells derived from the BAL of DR3+ LS patients. Using a deep-sequencing approach, we determined the TCRα and TCRβ chain usage as well as αβTCR pairs expressed on BAL CD4+ T cells from LS patients. TRAV12-1 and TRBV2 (formerly BV22) were the most expanded V region gene segments in DR3+ LS patients relative to control subjects, and TRAV12-1 and TRBV2 CDR3 motifs were shared between multiple DR3+ LS patients. When assessing αβTCR pairing, TRAV12-1 preferentially paired with TRBV2, and these TRAV12-1/TRBV2 TCRs displayed CDR3 homology. These findings suggest that public CD4+ T cell receptor repertoires exist amongst Löfgren’s syndrome patients and that these T cells are recognizing the putative sarcoidosis-associated antigen(s) in the context of HLA-DR3.
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DOI：
10.1073/pnas.1606994113
发表时间：
2016-07-19
影响因子：
11.1
作者：
Munson, Daniel J.;Egelston, Colt A.;Slansky, Jill E.
通讯作者：
Slansky, Jill E.
影响因子：
30.5
作者：
Frahm, N;Kiepiela, P;Brander, C
通讯作者：
Brander, C
影响因子：
24.3
作者：
Planck, A;Eklund, A;Grunewald, J
通讯作者：
Grunewald, J
影响因子：
4.8
作者：
Billam, Padma;Bonaparte, Kathryn L.;Graham, Barney S.
通讯作者：
Graham, Barney S.
影响因子：
7.7
作者：
Michels, Aaron W.;Landry, Laurie G.;Nakayama, Maki
通讯作者：
Nakayama, Maki