Zhang Yikai, Xu Ling, Chen Shaohua, Zha Xianfeng, Wei Wei, Li Yangqiu
1Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, 601 Huang Pu Da Dao Xi, 510632 Guangzhou, People's Republic of China.
2Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632 China.
Biomark Res. 2019 Jun 14;7:12. doi: 10.1186/s40364-019-0163-1. eCollection 2019.
We previously identified a 21 T cell clone which was specific to CML patients, and demonstrated that 13/21 gene-modified CD3 T cells had specific cytotoxicity for HLA-A11 K562 cells. However, it remains unclear which antigen is specifically recognized by the 21 T cell clone. In this study, CD3 T cells from healthy donor peripheral blood were stimulated with the WT1 peptide or mixed BCR-ABL peptides in the presence or absence of IL-2 and IL-7. The distribution of the repertoire was analyzed after different stimulations. We found that the mixed BCR-ABL peptides induced clonally expanded 7-9-2-2-7 T cells while the Wilms Tumor 1 peptide induced clonally expanded 11-2-1-1-1 T cells by high-throughput sequencing and GeneScan. Interestingly, the sequence and CDR3 motif of 11-2 T cell clone are similar to the 21 (a different region naming system) T cell clone that we previously found in CML patients. Thus, our findings suggest that the 21 T cell clone found in CML patients might be a T cell clone that specifically recognizes WT1.
我们之前鉴定出一个对慢性粒细胞白血病（CML）患者具有特异性的21个T细胞克隆，并证明13/21个基因修饰的CD3 T细胞对HLA - A11 K562细胞具有特异性细胞毒性。然而，目前尚不清楚21个T细胞克隆具体识别的是哪种抗原。在本研究中，在有或无白细胞介素 - 2（IL - 2）和白细胞介素 - 7（IL - 7）存在的情况下，用WT1肽或混合的BCR - ABL肽刺激来自健康供体外周血的CD3 T细胞。在不同刺激后分析库的分布。通过高通量测序和基因扫描，我们发现混合的BCR - ABL肽诱导了克隆性扩增的7 - 9 - 2 - 2 - 7 T细胞，而威尔姆斯瘤1肽诱导了克隆性扩增的11 - 2 - 1 - 1 - 1 T细胞。有趣的是，11 - 2 T细胞克隆的序列和互补决定区3（CDR3）基序与我们之前在CML患者中发现的21个（不同的区域命名系统）T细胞克隆相似。因此，我们的研究结果表明，在CML患者中发现的21个T细胞克隆可能是一个特异性识别WT1的T细胞克隆。
