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

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)