title: 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.
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.
authors: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Soyoko
authors: S
authors: Morimoto
authors: Yoshihiro
authors: Y
authors: Oka
authors: Akihiro
authors: A
authors: Tsuboi
authors: Yukie
authors: Y
authors: Tanaka
authors: Fumihiro
authors: F
authors: Fujiki
authors: Hiroko
authors: H
authors: Nakajima
authors: Naoki
authors: N
authors: Hosen
authors: Sumiyuki
authors: S
authors: Nishida
authors: Jun
authors: J
authors: Nakata
authors: Yoshiki
authors: Y
authors: Nakae
authors: Motohiko
authors: M
authors: Maruno
authors: Akira
authors: A
authors: Myoui
authors: Takayuki
authors: T
authors: Enomoto
authors: Shuichi
authors: S
authors: Izumoto
authors: Mitsugu
authors: M
authors: Sekimoto
authors: Naoki
authors: N
authors: Kagawa
authors: Naoya
authors: N
authors: Hashimoto
authors: Toshiki
authors: T
authors: Yoshimine
authors: Yusuke
authors: Y
authors: Oji
authors: Atsushi
authors: A
authors: Kumanogoh
authors: Haruo
authors: H
authors: Sugiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016162:Genes, Wilms Tumor; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta