title: Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein.
abstract: OBJECTIVE
  Human T-cell leukemia virus type I (HTLV-I) can cause an adult T-cell leukemia/lymphoma (ATLL). Because ATLL is a life-threatening lymphoproliferative disorder and is resistant to chemotherapy, the establishment and enhancement of T-cell immunity to HTLV-I through the development of therapeutic vaccines could be of value. Thus, the identification of HTLV-I epitopes for both CD8(+) and CD4(+) T cells should facilitate the development of effective vaccines. Although numerous HTLV-I epitopes for CTLs have been identified, few epitopes recognized by CD4(+) helper T cells against this virus have been described.
  
  
  METHODS
  Synthetic peptides prepared from several regions of the HTLV-I envelope (Env) sequence that were predicted to serve as helper T-cell epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro helper T-cell responses using lymphocytes from normal volunteers.
  
  
  RESULTS
  The results show that the HTLV-I-Env(317-331), and HTLV-I-Env(384-398)-reactive helper T lymphocytes restricted by HLA-DQw6 and HLA-DR15, respectively, could recognize intact HTLV-I+ T-cell lymphoma cells and, as a consequence, secrete lymphokines. In addition, HTLV-I Env(196-210)-reactive helper T lymphocytes restricted by HLA-DR9 were able to directly kill HTLV-I+ lymphoma cells and recognize naturally processed antigen derived from killed HTLV-I+ lymphoma cells, which was presented to the helper T cells by autologous antigen-presenting cells.
  
  
  CONCLUSIONS
  The present findings hold relevance for the design and optimization of T-cell epitope-based immunotherapy against HTLV-I-induced diseases such as ATLL.
authors.affiliation: Department of Pathology, Asahikawa Medical College, Asahikawa, Japan. hiroya@asahikawa-med.ac.jp
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yanai
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tateno
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Omiya
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
mesh_terms: D000465:Algorithms; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins
chemical_list: D000939:Epitopes; D014759:Viral Envelope Proteins