The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients.
The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients.
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DOI：
10.3390/ijms22052428
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发表时间：
2021-02-28
影响因子：
5.6
通讯作者：
Dai S
中科院分区：
文献类型：
--
作者：
Chen L;Zhang Y;Pacheco K;Dai S
镍（Ni 2+）是最常见的过敏原之一，影响约10-15%的普通人群。随着骨科植入物手术需求的增加，由于关节植入物失效而导致的手术翻修数量也在增加。有证据表明，一些患者由于对植入物成分的免疫反应而发生关节衰竭，我们发现Ni 2+是一个特别重要的原因。因此，了解镍2+过敏诱导关节植入失败的机制成为一个关键的研究问题。Ni 2+激活致病性T细胞的结构基础尚不清楚。本研究的目的是使用单细胞测序技术来表征来自由于Ni 2+致敏的关节衰竭患者的外周血的Ni 2+反应性T细胞库。我们在体外刺激来自两名植入失败患者的Ni 2+反应性T细胞的增殖，并将其分选用于单细胞VDJ测序（10×基因组学）。我们确定了2650生产V-J跨越对。TCR α链和β链均富集。TRBV 18使用率在P7 CD 4+群体中最高（18.1%），TRBV 5 -1使用率在P7 CD 8+群体中最高（12.1%）。TRBV 19和TRBV 20 -1区段存在于高百分比的P7和P9测序的T细胞中。值得注意的是，TRAV 41-TRBV 18的α和β链组合占P7患者的CD 4+群体的13.5%。与目前接触性皮炎的Ni特异性T细胞库研究相比，这些关节植入失败患者的Vα和Vβ使用情况不同。这可能是由于这两种不同组织中自身肽的不同可用性。然而，TRBV 19（Vβ17）是最常用的TCR β链之一，在以往的报道中很常见。这意味着一些致病性T细胞在皮肤和关节中的Ni 2+超敏反应中可能是相似的。TCR CDR 3 β序列的比对显示，保守的谷氨酸（Glu）可能与Ni 2+相互作用。对这些Ni 2+特异性TCR的研究可能有助于阐明低分子量化学半抗原激活T细胞的分子机制。
Nickel (Ni2+) is one of the most common allergens, affecting around 10–15% of the general population. As the demand for orthopedic implant surgery rises, the number of surgical revisions due to joint implant failure also increases. There is evidence that some patients develop joint failure due to an immune response to a component of the implant, and we have found that Ni2+ is an especially important cause. Hence, understanding the mechanisms by which Ni2+ allergy induces joint implant failure becomes a critical research question. The structural basis of Ni2+ activation of pathogenic T cells is still not clear. The purpose of this study was to characterize Ni2+-reactive T cell repertoires derived from the peripheral blood of joint failure patients due to Ni2+ sensitization using single-cell sequencing techniques. We stimulated the proliferation of Ni2+ -reactive T cells from two implant failure patients in vitro, and sorted them for single-cell VDJ sequencing (10× genomics). We identified 2650 productive V-J spanning pairs. Both TCR α chains and β chains were enriched. TRBV18 usage is the highest in the P7 CD4+ population (18.1%), and TRBV5-1 usage is the highest in the P7 CD8+ population (12.1%). TRBV19 and TRBV20-1 segments are present in a high percentage of both P7 and P9 sequenced T cells. Remarkably, the alpha and beta chain combination of TRAV41-TRBV18 accounts for 13.5% of the CD4+ population of P7 patient. Compared to current Ni specific T cell repertoire studies of contact dermatitis, the Vα and Vβ usages of these joint implant failure patients were different. This could be due to the different availability of self-peptides in these two different tissues. However, TRBV19 (Vβ17) was among frequently used TCR β chains, which are common in previous reports. This implies that some pathogenic T cells could be similar in Ni2+ hypersensitivities in skin and joints. The alignment of the TCR CDR3β sequences showed a conserved glutamic acid (Glu) that could potentially interact with Ni2+. The study of these Ni2+ specific TCRs may shed light on the molecular mechanism of T cell activation by low molecular weight chemical haptens.
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影响因子：
4.4
作者：
Vollmer, J;Weltzien, HU;Moulon, C
通讯作者：
Moulon, C
DOI：
10.1084/jem.20021762
发表时间：
2003-03-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lu L;Vollmer J;Moulon C;Weltzien HU;Marrack P;Kappler J
通讯作者：
Kappler J
影响因子：
158.5
作者：
Ostendorf, Lennard;Burns, Marie;Alexander, Tobias
通讯作者：
Alexander, Tobias
影响因子：
--
作者：
Adala, Raviraj;Chakravarthy, Murali;Pai, Sanjay
通讯作者：
Pai, Sanjay
影响因子：
5.4
作者：
Vollmer, J;Fritz, M;Moulon, C
通讯作者：
Moulon, C