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

Overview

Journal Cancer Sci

Specialty Oncology

Date 2011 Dec 1

PMID 22126448

Citations 3

Authors

Soyoko Morimoto

Yoshihiro Oka

Akihiro Tsuboi

Yukie Tanaka

Fumihiro Fujiki

Hiroko Nakajima

Naoki Hosen

Sumiyuki Nishida

Jun Nakata

Yoshiki Nakae

Motohiko Maruno

Akira Myoui

Takayuki Enomoto

Shuichi Izumoto

Mitsugu Sekimoto

Naoki Kagawa

Naoya Hashimoto

Toshiki Yoshimine

Yusuke Oji

Atsushi Kumanogoh

Haruo Sugiyama

Affiliations

Soon will be listed here.

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 WT1(126) peptide (amino acids 126-134, WT1(126))-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 WT1(126)-specific CTLs at the single cell level. Usage analysis with single-cell RT-PCR of TCR-BV gene families of individual FACS-sorted WT1(126) 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.

Citing Articles

Spontaneous high clonal expansion of Wilms' tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms' tumor gene 1-expressing solid tumor.

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Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma.

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Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican‑3‑derived peptide.

Tada Y, Yoshikawa T, Shimomura M, Sawada Y, Sakai M, Shirakawa H Int J Oncol. 2013; 43(4):1019-26.

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