Universal cytotoxic activity of a HTLV-1 Tax-specific T cell clone from an HLA-A*24:02+ patient with adult T-cell leukemia against a variety of HTLV-I-infected T-cells

Yukie Tanaka, Rie Yamazaki, Kiriko Terasako-Saito, Hideki Nakasone, Yu Akahoshi, Hirofumi Nakano, Tomotaka Ugai, Hidenori Wada, Ryoko Yamasaki, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Masahiro Ashizawa, Miki Sato, Shun ichi Kimura, Misato Kikuchi, Shinichi Kako, Junya Kanda, Aki Tanihara, Junji NishidaYoshinobu Kanda

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Abstract

Adult T cell leukemia/lymphoma (ATL) is an aggressive mature T cell malignancy that is causally associated with human T cell lymphotropic virus type 1 (HTLV-1) infection. The HTLV-1 regulatory protein Tax aggressively accelerates the proliferation of host cells and is also an important target antigen for CD8+ cytotoxic T cells (CTLs). We previously reported that several predominant HLA-A*24:02-restricted HTLV-1 Tax301-309-specific CTL clones commonly expressed a particular amino acid sequence motif (P-D-R) in complementarity-determining region 3 of T-cell receptor (TCR)-β chain among unrelated ATL patients who underwent allogeneic stem cell transplantation (allo-HSCT). Furthermore, a PDR-motif+ CTL clone persistently existed in a long-term survivor as a central CTL clone with strong CTL activities after HSCT. Although a larger analysis of the relationship between PDR-motif+ CTLs and the clinical course is required, the expression of PDR-motif+ TCR on CD8+ T cells may play a critical role in the management of anti-HTLV-1 activities for HLA-A24:02+ ATL patients. Therefore, in this study, we prepared an HTLV-1 Tax301-309 peptide-specific CTL clone (HT-9) expressing PDR-motif+ TCR isolated from a long-term survivor after HSCT, and evaluated its CTL activity against a variety of HTLV-1-infected T-cells from HLA-A*24:02+ ATL patients. Before the assay of CTL function, we confirmed that HT-9 expressed less-differentiated effector-memory phenotypes (CD45RA-CCR7-CD27+CD28+/-CD57+/-) and T-cell exhaustion marker PD-1+. In assays of CTL function, HT-9 recognized HTLV-1 Tax in an HLA-restricted fashion and demonstrated strong CTL activities against a variety of HTLV-1-infected T-cells from HLA-A*24:02+ ATL patients regardless of whether the sources were autologous or allogeneic, but not normal cells. These data indicate that PDR-motif+ TCR could be an important TCR candidate for TCR-gene immunotherapy for HLA-A24:02+ ATL patients, provided that the CTL activities against HTLV-1 are reproduced in in vivo experiments using mouse models.

Original languageEnglish
Pages (from-to)120-125
Number of pages6
JournalImmunology Letters
Volume158
Issue number1-2
DOIs
Publication statusPublished - 2014 Mar 1

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Keywords

  • Adult T cell leukemia/lymphoma
  • Human T cell lymphotropic virus type 1
  • Immunotherapy
  • T-cell receptor
  • Tax

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tanaka, Y., Yamazaki, R., Terasako-Saito, K., Nakasone, H., Akahoshi, Y., Nakano, H., Ugai, T., Wada, H., Yamasaki, R., Ishihara, Y., Kawamura, K., Sakamoto, K., Ashizawa, M., Sato, M., Kimura, S. I., Kikuchi, M., Kako, S., Kanda, J., Tanihara, A., ... Kanda, Y. (2014). Universal cytotoxic activity of a HTLV-1 Tax-specific T cell clone from an HLA-A*24:02+ patient with adult T-cell leukemia against a variety of HTLV-I-infected T-cells. Immunology Letters, 158(1-2), 120-125. https://doi.org/10.1016/j.imlet.2013.12.016