title: HTLV-1 bZIP factor-specific CD4 T cell responses in adult T cell leukemia/lymphoma patients after allogeneic hematopoietic stem cell transplantation.
abstract: We document human T lymphotropic virus type 1 (HTLV-1) bZIP factor (HBZ)-specific CD4 T cell responses in an adult T cell leukemia/lymphoma (ATL) patient after allogeneic hematopoietic stem cell transplantation (HCT) and identified a novel HLA-DRB1*15:01-restricted HBZ-derived naturally presented minimum epitope sequence, RRRAEKKAADVA (HBZ114-125). This peptide was also presented on HLA-DRB1*15:02, recognized by CD4 T cells. Notably, HBZ-specific CD4 T cell responses were only observed in ATL patients after allogeneic HCT (4 of 9 patients) and not in nontransplanted ATL patients (0 of 10 patients) or in asymptomatic HTLV-1 carriers (0 of 10 carriers). In addition, in one acute-type patient, HBZ-specific CD4 T cell responses were absent in complete remission before HCT, but they became detectable after allogeneic HCT. We surmise that HTLV-1 transmission from mothers to infants through breast milk in early life induces tolerance to HBZ and results in insufficient HBZ-specific T cell responses in HTLV-1 asymptomatic carriers or ATL patients. In contrast, after allogeneic HCT, the reconstituted immune system from donor-derived cells can recognize virus protein HBZ as foreign, and HBZ-specific immune responses are provoked that contribute to the graft-versus-HTLV-1 effect.
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;
authors.forename: Tomoko
authors.initials: T
authors.lastname: Narita
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Ayako
authors.initials: A
authors.lastname: Masaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Asahi
authors.initials: A
authors.lastname: Ito
authors.forename: Fumiko
authors.initials: F
authors.lastname: Mori
authors.forename: Tomiko
authors.initials: T
authors.lastname: Yamada
authors.forename: Masaki
authors.initials: M
authors.lastname: Ri
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
mesh_terms: D064591:Allografts; D000595:Amino Acid Sequence; D058070:Asymptomatic Diseases; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002353:Carrier State / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D005838:Genotype; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology; D015486:HTLV-I Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000601:surgery; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D012191:Retroviridae Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D018984:Epitopes, T-Lymphocyte; C479751:HBZ protein, human T-cell leukemia virus type I; D006681:HLA-D Antigens; D015486:HTLV-I Antigens; D010446:Peptide Fragments; D012191:Retroviridae Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D007371:Interferon-gamma