A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope

Hiroya Kobayashi, Takumi Kumai, Satoshi Hayashi, Yoshinari Matsuda, Naoko Aoki, Keisuke Sato, Shoji Kimura, Esteban Celis

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1- transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH2-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+ T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/ lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.

Original languageEnglish (US)
Pages (from-to)2215-2225
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume61
Issue number12
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Fingerprint

Interleukin-9 Receptors
Deltaretrovirus
HLA-DR Antigens
Epitopes
Adult T Cell Leukemia Lymphoma
T-Cell Lymphoma
T-Lymphocytes
Peptides
CD4 Antigens
Peptide T
T-Cell Leukemia
T-Lymphocyte Epitopes
Reverse-Phase Chromatography
Helper-Inducer T-Lymphocytes
Immunotherapy
Immunity
Vaccines
High Pressure Liquid Chromatography

Keywords

  • Adult T cell leukemia/lymphoma
  • CD4 helper T lymphocytes
  • HTLV-1
  • IL-9 receptor
  • Major histocompatibility complex class II
  • Tumor antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope. / Kobayashi, Hiroya; Kumai, Takumi; Hayashi, Satoshi; Matsuda, Yoshinari; Aoki, Naoko; Sato, Keisuke; Kimura, Shoji; Celis, Esteban.

In: Cancer Immunology, Immunotherapy, Vol. 61, No. 12, 01.12.2012, p. 2215-2225.

Research output: Contribution to journalArticle

Kobayashi, Hiroya ; Kumai, Takumi ; Hayashi, Satoshi ; Matsuda, Yoshinari ; Aoki, Naoko ; Sato, Keisuke ; Kimura, Shoji ; Celis, Esteban. / A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope. In: Cancer Immunology, Immunotherapy. 2012 ; Vol. 61, No. 12. pp. 2215-2225.
@article{886687a1f176495d87003444e648231c,
title = "A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope",
abstract = "Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1- transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH2-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+ T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/ lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.",
keywords = "Adult T cell leukemia/lymphoma, CD4 helper T lymphocytes, HTLV-1, IL-9 receptor, Major histocompatibility complex class II, Tumor antigens",
author = "Hiroya Kobayashi and Takumi Kumai and Satoshi Hayashi and Yoshinari Matsuda and Naoko Aoki and Keisuke Sato and Shoji Kimura and Esteban Celis",
year = "2012",
month = "12",
day = "1",
doi = "10.1007/s00262-012-1284-7",
language = "English (US)",
volume = "61",
pages = "2215--2225",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "12",

}

TY - JOUR

T1 - A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope

AU - Kobayashi, Hiroya

AU - Kumai, Takumi

AU - Hayashi, Satoshi

AU - Matsuda, Yoshinari

AU - Aoki, Naoko

AU - Sato, Keisuke

AU - Kimura, Shoji

AU - Celis, Esteban

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1- transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH2-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+ T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/ lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.

AB - Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1- transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH2-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+ T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/ lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.

KW - Adult T cell leukemia/lymphoma

KW - CD4 helper T lymphocytes

KW - HTLV-1

KW - IL-9 receptor

KW - Major histocompatibility complex class II

KW - Tumor antigens

UR - http://www.scopus.com/inward/record.url?scp=84871021426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871021426&partnerID=8YFLogxK

U2 - 10.1007/s00262-012-1284-7

DO - 10.1007/s00262-012-1284-7

M3 - Article

C2 - 22638550

AN - SCOPUS:84871021426

VL - 61

SP - 2215

EP - 2225

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 12

ER -