文章：

CD8+/TCRαβ+ T细胞大颗粒淋巴细胞白血病缺乏常见的TCRA和TCRB克隆型：抗原选择在CD8+ T-LGL免疫发病机制中的作用综述

Lack of common TCRA and TCRB clonotypes in CD8+/TCRαβ+ T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8+ T-LGL

原文发布日期：2014-01-10

DOI: 10.1038/bcj.2013.70

类型: Original Article

开放获取: 是

英文摘要：

Clonal CD8⁺/T-cell receptor (TCR)αβ⁺ T-cell large granular lymphocyte (T-LGL) proliferations constitute the most common subtype of T-LGL leukemia. Although the etiology of T-LGL leukemia is largely unknown, it has been hypothesized that chronic antigenic stimulation contributes to the pathogenesis of this disorder. In the present study, we explored the association between expanded TCR-Vβ and TCR-Vα clonotypes in a cohort of 26 CD8⁺/TCRαβ⁺ T-LGL leukemia patients, in conjunction with the HLA-ABC genotype, to find indications for common antigenic stimuli. In addition, we applied purpose-built sophisticated computational tools for an in-depth evaluation of clustering of TCRβ (TCRB) complementarity determining region 3 (CDR3) amino-acid LGL clonotypes. We observed a lack of clear TCRA and TCRB CDR3 homology in CD8⁺/TCRαβ⁺ T-LGL, with only low level similarity between small numbers of cases. This is in strong contrast to the homology that is seen in CD4⁺/TCRαβ⁺ T-LGL and TCRγδ⁺ T-LGL and thus underlines the idea that the LGL types have different etiopathogenesis. The heterogeneity of clonal CD8⁺/TCRαβ⁺ T-LGL proliferations might in fact suggest that multiple pathogens or autoantigens are involved.

摘要翻译： 

克隆性CD8⁺/T细胞受体（TCR）αβ⁺ T细胞大颗粒淋巴细胞（T-LGL）增殖构成T-LGL白血病最常见亚型。尽管T-LGL白血病的病因尚不明确，但学界推测慢性抗原刺激参与该疾病的发病机制。本研究通过分析26例CD8⁺/TCRαβ⁺ T-LGL白血病患者的TCR-Vβ和TCR-Vα克隆扩增与HLA-ABC基因型的关联，以寻找共同抗原刺激的迹象。此外，我们应用专门设计的复杂计算工具深度评估TCRβ（TCRB）互补决定区3（CDR3）氨基酸序列中LGL克隆型的聚类特征。研究发现CD8⁺/TCRαβ⁺ T-LGL缺乏明显的TCRA和TCRB CDR3同源性，仅少数病例间存在低水平相似性。这与CD4⁺/TCRαβ⁺ T-LGL及TCRγδ⁺ T-LGL中观察到的同源性形成鲜明对比，从而印证了不同类型LGL具有不同发病机制的观点。克隆性CD8⁺/TCRαβ⁺ T-LGL增殖的异质性实际上可能提示多种病原体或自身抗原参与其中。

原文链接：

Lack of common TCRA and TCRB clonotypes in CD8+/TCRαβ+ T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8+ T-LGL