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

Abstract

Abstract We previously identified a TCR Vβ21 T cell clone which was specific to CML patients, and demonstrated that TCR Vα13/β21 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 Vβ21 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 Vβ7–9-Dβ2-Jβ2–7 T cells while the Wilms Tumor 1 peptide induced clonally expanded Vβ11–2-Dβ1-Jβ1–1 T cells by high-throughput TCRβ sequencing and GeneScan. Interestingly, the sequence and CDR3 motif of Vβ11–2 T cell clone are similar to the TCR Vβ21 (a different TCR V region naming system) T cell clone that we previously found in CML patients. Thus, our findings suggest that the TCR Vβ21 T cell clone found in CML patients might be a T cell clone that specifically recognizes WT1.

Keywords

• Chronic myelogenous leukemia
• Wilms tumor 1
• BCR-ABL
• T cell repertoire
• T-cell receptor beta-chain sequencing