Single-cell analysis of T-cell receptor repertoire of HTLV-1 Tax-specific cytotoxic T cells in allogeneic transplant recipients with adult T-cell leukemia/lymphoma

Cancer Research
Yukie TanakaYoshinobu Kanda

Abstract

Adult T-cell leukemia (ATL) is a lymphoproliferative malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. Recently, it has been shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for ATL, and that HTLV-1 Tax-specific CD8(+) cytotoxic T cells (CTL) contribute to the graft-versus-ATL effect. In the present study, we, for the first time, analyzed the T-cell receptor (TCR) repertoire of isolated Tax(301-309) (SFHSLHLLF)-specific CTLs in HLA-A*2402(+) ATL patients before and after allo-HSCT by single-cell reverse transcription-PCR. The Tax(301-309)-specific CTLs in bone marrow and peripheral blood showed highly restricted oligoclonal diversity. In addition, a unique conserved amino acid motif of "P-D/P-R" in TCR-beta complementarity-determining region 3 in either BV7- or BV18-expressing CTLs was observed not only in all of the samples from ATL patients, but also in samples from the same patient before and after HSCT. Furthermore, the P-D/P-R motif-bearing CTL clones established from peripheral blood samples after HSCT exhibited strong killing activity against the HTLV-1-infected T cells of the patient. CTL clones were not established in vitro from samp...Continue Reading

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Citations

Jan 22, 2013·Nature Biotechnology·Brandon J DeKoskyGeorge Georgiou
Jan 23, 2016·Frontiers in Molecular Biosciences·Georgios S E Antipas, Anastasios E Germenis
Nov 29, 2014·Transplant Infectious Disease : an Official Journal of the Transplantation Society·K Terasako-SaitoY Kanda
May 7, 2016·Viruses·Angela CiuffiAmalio Telenti
Nov 7, 2016·Virus Research·Sylvie RatoAngela Ciuffi
Apr 21, 2020·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Koji KawamuraYoshinobu Kanda

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