title: In vitro peptide immunization of target tax protein human T-cell leukemia virus type 1-specific CD4+ helper T lymphocytes.
abstract: OBJECTIVE
  Adult T-cell leukemia/lymphoma induced by human T-cell leukemia virus type 1 (HTLV-1) is usually a fatal lymphoproliferative malignant disease. HTLV-1 Tax protein plays a critical role in HTLV-1-associated leukemogenesis and is an attractive target for vaccine development. Although HTLV-1 Tax is the most dominant antigen for HTLV-1-specific CD8(+) CTLs in HTLV-1-infected individuals, few epitopes recognized by CD4(+) helper T lymphocytes in HTLV-1 Tax protein have been described. The aim of the present study was to study T-helper-cell responses to HTLV-1 Tax and to identify naturally processed MHC class II-restricted epitopes that could be used for vaccine development.
  
  
  METHODS
  An MHC class II binding peptide algorithm was used to predict potential T-helper cell epitope peptides from HTLV-1 Tax. We assessed the ability of the corresponding peptides to elicit helper T-cell responses by in vitro vaccination of purified CD4(+) T lymphocytes.
  
  
  RESULTS
  Peptides Tax(191-205) and Tax(305-319) were effective in inducing T-helper-cell responses. Although Tax(191-205) was restricted by the HLA-DR1 and DR9 alleles, responses to Tax(305-319) were restricted by either DR15 or DQ9. Both these epitopes were found to be naturally processed by HTLV-1(+) T-cell lymphoma cells and by autologous antigen-presenting cells that were pulsed with HTLV-1 Tax(+) tumor lysates. Notably, the two newly identified helper T-cell epitopes are found to lie proximal to known CTL epitopes, which will facilitate the development of prophylactic peptide-based vaccine capable of inducing simultaneous CTL and T-helper responses.
  
  
  CONCLUSIONS
  Our data suggest that HTLV-1 Tax protein could serve as tumor-associated antigen for CD4(+) helper T cells and that the present epitopes might be used for T-cell-based immunotherapy against tumors expressing HTLV-1.
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: Ngato
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Naoko
authors.initials: N
authors.lastname: Aoki
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aizawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tateno
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D016356:Gene Products, tax / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016356:Gene Products, tax; D006681:HLA-D Antigens; D010455:Peptides