Yin Qingsong, Tan Huo, Chen Shaohua, Yang Lijian, Ye Jingmei, Li Yangqiu
Institute of Hematology, Jinan University, Guangzhou, China.
Hematology. 2010 Feb;15(1):48-57. doi: 10.1179/102453310X12583347009694.
T-cell immunodeficiency is a common feature in cancer patients, but clonally expanded T cells which were considered to have the specific anti-tumor cytotoxicity can be identified in most cancer patients, including those with hematological malignancies. We previously reported that there were skewed usages of T-cell receptor (TCR) Valpha and TCR Vbeta subfamily in clonally expanded T cells in the peripheral blood (PB) of patients with diffuse large B-cell lymphoma (DLBCL). In order to investigate the characteristics of the complementarity determining region 3 (CDR3) of TCR alpha- and beta-chain genes in clonally expanded T cells, the sequences of TCR-CDR3 region of clonally expanded TCR Valpha and TCR Vbeta subfamily T cells were analyzed. Conserved amino acid motifs of TCR-CDR3 region were identified in different clonally expanded T cells. RSxYNTDKLI, SxGG, GGS, and DSxY motifs were found in the TCR Valpha subfamily T-cell clones, while SxGTG, SRG, and GTxD motifs existed in the TCR Vbeta subfamily T-cell clones. Moreover, the TCR harboring conserved motif in CDR3 region of some T-cell clones had high homology in the three-dimensional spatial structures. These findings revealed the mono/oligoclonally expanded T cells were derived from the stimulation of some antigens in the PB of patients with DLBCL, and may be recognizing an identical antigenic epitope.
T细胞免疫缺陷是癌症患者的常见特征，但在大多数癌症患者中，包括血液系统恶性肿瘤患者，都可以识别出被认为具有特异性抗肿瘤细胞毒性的克隆性扩增T细胞。我们之前报道过，弥漫性大B细胞淋巴瘤（DLBCL）患者外周血（PB）中克隆性扩增的T细胞存在T细胞受体（TCR）Vα和TCR Vβ亚家族的偏态使用。为了研究克隆性扩增T细胞中TCRα和β链基因互补决定区3（CDR3）的特征，对克隆性扩增的TCR Vα和TCR Vβ亚家族T细胞的TCR-CDR3区域序列进行了分析。在不同的克隆性扩增T细胞中鉴定出了TCR-CDR3区域的保守氨基酸基序。在TCR Vα亚家族T细胞克隆中发现了RSxYNTDKLI、SxGG、GGS和DSxY基序，而在TCR Vβ亚家族T细胞克隆中存在SxGTG、SRG和GTxD基序。此外，一些T细胞克隆的CDR3区域含有保守基序的TCR在三维空间结构上具有高度同源性。这些发现揭示了单克隆/寡克隆扩增的T细胞源自DLBCL患者PB中某些抗原的刺激，并且可能识别相同的抗原表位。
