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.
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.
Tanaka
Yukie
Y
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama, Japan.
Nakasone
Hideki
H
Yamazaki
Rie
R
Sato
Ken
K
Sato
Miki
M
Terasako
Kiriko
K
Kimura
Shun-ichi
S
Okuda
Shinya
S
Kako
Shinichi
S
Oshima
Kumi
K
Tanihara
Aki
A
Nishida
Junji
J
Yoshikawa
Toshiaki
T
Nakatsura
Tetsuya
T
Sugiyama
Haruo
H
Kanda
Yoshinobu
Y
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
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