Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein

Hiroya Kobayashi, Toshihiro Nagato, Mitsuru Yanai, Kensuke Oikawa, Keisuke Sato, Shoji Kimura, Masatoshi Tateno, Ryusuke Omiya, Esteban Celis

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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-Env317-331, 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.

Original languageEnglish (US)
Pages (from-to)7053-7062
Number of pages10
JournalClinical Cancer Research
Volume10
Issue number20
DOIs
StatePublished - Oct 15 2004
Externally publishedYes

Fingerprint

Viral Envelope Proteins
Adult T Cell Leukemia Lymphoma
Human T-lymphotropic virus 1
Helper-Inducer T-Lymphocytes
Epitopes
T-Lymphocyte Epitopes
Lymphoma
Vaccines
T-Lymphocytes
Lymphoproliferative Disorders
T-Cell Lymphoma
Lymphokines
Autoantigens
Antigen-Presenting Cells
Immunotherapy
Immunity
Healthy Volunteers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein. / Kobayashi, Hiroya; Nagato, Toshihiro; Yanai, Mitsuru; Oikawa, Kensuke; Sato, Keisuke; Kimura, Shoji; Tateno, Masatoshi; Omiya, Ryusuke; Celis, Esteban.

In: Clinical Cancer Research, Vol. 10, No. 20, 15.10.2004, p. 7053-7062.

Research output: Contribution to journalArticle

Kobayashi, Hiroya ; Nagato, Toshihiro ; Yanai, Mitsuru ; Oikawa, Kensuke ; Sato, Keisuke ; Kimura, Shoji ; Tateno, Masatoshi ; Omiya, Ryusuke ; Celis, Esteban. / Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 20. pp. 7053-7062.
@article{da5cb7a0e2384ddc96ff17991835df49,
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 = "Purpose: 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. Experimental Design: 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-Env317-331, 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.",
author = "Hiroya Kobayashi and Toshihiro Nagato and Mitsuru Yanai and Kensuke Oikawa and Keisuke Sato and Shoji Kimura and Masatoshi Tateno and Ryusuke Omiya and Esteban Celis",
year = "2004",
month = "10",
day = "15",
doi = "10.1158/1078-0432.CCR-04-0897",
language = "English (US)",
volume = "10",
pages = "7053--7062",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

T1 - Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein

AU - Kobayashi, Hiroya

AU - Nagato, Toshihiro

AU - Yanai, Mitsuru

AU - Oikawa, Kensuke

AU - Sato, Keisuke

AU - Kimura, Shoji

AU - Tateno, Masatoshi

AU - Omiya, Ryusuke

AU - Celis, Esteban

PY - 2004/10/15

Y1 - 2004/10/15

N2 - Purpose: 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. Experimental Design: 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-Env317-331, 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.

AB - Purpose: 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. Experimental Design: 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-Env317-331, 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.

UR - http://www.scopus.com/inward/record.url?scp=6044233329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6044233329&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-04-0897

DO - 10.1158/1078-0432.CCR-04-0897

M3 - Article

VL - 10

SP - 7053

EP - 7062

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 20

ER -