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 Scopus citations

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

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

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