In vitro peptide immunization of target tax protein human T-cell leukemia virus type 1-specific CD4+ helper T lymphocytes

Hiroya Kobayashi, Toshihiro Ngato, Keisuke Sato, Naoko Aoki, Shoji Kimura, Yuetsu Tanaka, Hitoshi Aizawa, Masatoshi Tateno, Esteban Celis

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Experimental Design: 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 Tax191-205 and Tax305-319 were effective in inducing T-helper-cell responses. Although Tax 191-205 was restricted by the HLA-DR1 and DR9 alleles, responses to TaX305-319 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)3814-3822
Number of pages9
JournalClinical Cancer Research
Volume12
Issue number12
DOIs
StatePublished - Jun 15 2006

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tax Gene Products
Deltaretrovirus
Helper-Inducer T-Lymphocytes
Immunization
Peptides
T-Lymphocyte Epitopes
Epitopes
Deltaretrovirus Antigens
In Vitro Techniques
Vaccines
HLA-DR1 Antigen
Peptide T
T-Lymphocytes
Adult T Cell Leukemia Lymphoma
Subunit Vaccines
T-Cell Lymphoma
Autoantigens
Neoplasm Antigens
Antigen-Presenting Cells
Immunotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

In vitro peptide immunization of target tax protein human T-cell leukemia virus type 1-specific CD4+ helper T lymphocytes. / Kobayashi, Hiroya; Ngato, Toshihiro; Sato, Keisuke; Aoki, Naoko; Kimura, Shoji; Tanaka, Yuetsu; Aizawa, Hitoshi; Tateno, Masatoshi; Celis, Esteban.

In: Clinical Cancer Research, Vol. 12, No. 12, 15.06.2006, p. 3814-3822.

Research output: Contribution to journalArticle

Kobayashi, Hiroya ; Ngato, Toshihiro ; Sato, Keisuke ; Aoki, Naoko ; Kimura, Shoji ; Tanaka, Yuetsu ; Aizawa, Hitoshi ; Tateno, Masatoshi ; Celis, Esteban. / In vitro peptide immunization of target tax protein human T-cell leukemia virus type 1-specific CD4+ helper T lymphocytes. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 12. pp. 3814-3822.
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AU - Kobayashi, Hiroya

AU - Ngato, Toshihiro

AU - Sato, Keisuke

AU - Aoki, Naoko

AU - Kimura, Shoji

AU - Tanaka, Yuetsu

AU - Aizawa, Hitoshi

AU - Tateno, Masatoshi

AU - Celis, Esteban

PY - 2006/6/15

Y1 - 2006/6/15

N2 - Purpose: 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. Experimental Design: 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 Tax191-205 and Tax305-319 were effective in inducing T-helper-cell responses. Although Tax 191-205 was restricted by the HLA-DR1 and DR9 alleles, responses to TaX305-319 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. Conclusion: 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.

AB - Purpose: 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. Experimental Design: 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 Tax191-205 and Tax305-319 were effective in inducing T-helper-cell responses. Although Tax 191-205 was restricted by the HLA-DR1 and DR9 alleles, responses to TaX305-319 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. Conclusion: 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.

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