• Open Access

Biased usage of T cell receptor β-chain variable region genes of Wilms’ tumor gene (WT1)-specific CD8+ T cells in patients with solid tumors and healthy donors

Authors


13To whom correspondence should be addressed.
E-mail: sugiyama@sahs.med.osaka-u.ac.jp

Abstract

Wilms’ tumor gene 1 (WT1) protein is a promising tumor-associated antigen. In patients with WT1-expressing malignancies, WT1-specific CTLs are spontaneously induced as a result of an immune response to the WT1 protein. In the present study, we performed single cell-level comparative analysis of T cell receptor β-chain variable region (TCR-BV) gene families of a total of 750 spontaneously induced WT1126 peptide (amino acids 126–134, WT1126)-specific CTLs in both HLA-A*0201+ patients with solid tumors and healthy donors (HDs). This is the first report of direct usage analysis of 24 kinds of TCR-BV gene families of WT1126-specific CTLs at the single cell level. Usage analysis with single-cell RT-PCR of TCR-BV gene families of individual FACS-sorted WT1126 tetramer+ CD8+ T cells showed, for the first time, that: (i) BVs 3, 6, 7, 20, 27, and 28 were commonly biased in patients and HDs; (ii) BVs 2, 11, and 15 were biased only in patients; and (iii) BVs 4, 5, 9, and 19 were biased only in HDs. However, statistical analysis of similarity of individual usage frequencies of 24 kinds of TCR-BV gene families between patients and HDs indicated that the usage frequencies of TCR-BV gene families in patients reflected those in HDs. These results should provide us with a novel insight for a better understanding of WT1-specific immune responses. (Cancer Sci 2012; 103: 408–414)

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