Identification of TCR Vβ11-2-Dβ1-Jβ1-1 T cell clone specific for WT1 peptides using high-throughput TCRβ gene sequencing

Abstract

We previously identified a TCR Vβ 21 T cell clone which was specific to CML patients, and demonstrated that TCR Vα 13/ β 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 TCR Vβ 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 TCR Vβ repertoire was analyzed after different stimulations. We found that the mixed BCR-ABL peptides induced clonally expanded Vβ 7–9- Dβ 2- Jβ 2–7 T cells while the Wilms Tumor 1 peptide induced clonally expanded Vβ 11–2- Dβ 1- Jβ 1–1 T cells by high-throughput TCRβ sequencing and GeneScan. Interestingly, the sequence and CDR3 motif of Vβ 11–2 T cell clone are similar to the TCR Vβ 21 (a different TCR V region naming system) T cell clone that we previously found in CML patients. Thus, our findings suggest that the TCR Vβ 21 T cell clone found in CML patients might be a T cell clone that specifically recognizes WT1. Electronic supplementary material The online version of this article (10.1186/s40364-019-0163-1) contains supplementary material, which is available to authorized users.

Predictive value of TCR Vβ-Jβ profile for adjuvant gefitinib in EGFR mutant NSCLC from ADJUVANT-CTONG 1104 trial

“…Interestingly, Echchakir et al have reported high frequencies of Vβ5, Vβ20, and Vβ24 in patients with NSCLC ( 38 ). A previous work of ours demonstrated predominant expanded Vβ20-1 and Vβ29-1 in healthy human CD3 + T cells after WT1-specific antigen peptide or antigen BCR-ABL peptides induction ( 39 ). Notably, Vβ5 clone CD8 + T cells were related to antitumor activity in melanoma ( 40 ).…”

TCR engineered T cells for solid tumor immunotherapy

“…Our team and other researchers have found that specific TCR Vβ clones may recognize leukemia-associated antigens in leukemia patients by polymerase chain reaction (PCR) and GeneScan. We also discovered that our previously identified chronic myeloid leukemia (CML)-associated TCR Vβ clone specifically recognizes Wilm’s tumor 1 (WT1) antigenic peptides by stimulating T cells in healthy donors with MHC-restricted antigenic peptides and TCR Vβ gene sequencing [ 26 ]. Recently, our team and partners have also found TCR Vβ clones that are closely related to the prognosis of lung cancer patients [ 27 ].…”