title: 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.
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 samples prior to allo-HSCT. In addition, CTL clones with a strong killing activity were enriched in vivo after HSCT in the patient. Hence, Tax(301-309)-specific CTLs in ATL patients might have a preference for TCR construction and induce strong immune responses against the HTLV-1-infected T cells of patients, which contribute to the graft-versus-ATL effects after allo-HSCT. However, further analyses with a larger number of patients and more frequent sampling after allo-HSCT is required to confirm these findings.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.forename: Rie
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Miki
authors.initials: M
authors.lastname: Sato
authors.forename: Kiriko
authors.initials: K
authors.lastname: Terasako
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Kimura
authors.forename: Shinya
authors.initials: S
authors.lastname: Okuda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kako
authors.forename: Kumi
authors.initials: K
authors.lastname: Oshima
authors.forename: Aki
authors.initials: A
authors.lastname: Tanihara
authors.forename: Junji
authors.initials: J
authors.lastname: Nishida
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D020816:Amino Acid Motifs; D016356:Gene Products, tax / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D018380:Hematopoietic Stem Cell Transplantation; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000628:therapy / Q000821:virology; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D016356:Gene Products, tax; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C514970:tax protein, Human T-lymphotrophic virus 1