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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

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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.

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Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1, Asahikawa, 078-8510, Japan

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

  2. H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, SRB2, Tampa, FL, 33612, USA

    Esteban Celis

Authors
  1. Hiroya Kobayashi
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  2. Takumi Kumai
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  3. Satoshi Hayashi
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  4. Yoshinari Matsuda
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  5. Naoko Aoki
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  6. Keisuke Sato
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  7. Shoji Kimura
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  8. Esteban Celis
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Corresponding authors

Correspondence to Hiroya Kobayashi or Esteban Celis.

Additional information

Hiroya Kobayashi and Takumi Kumai contributed equally to this work.

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Kobayashi, H., Kumai, T., Hayashi, S. et al. 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. Cancer Immunol Immunother 61, 2215–2225 (2012). https://doi.org/10.1007/s00262-012-1284-7

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  • DOI: https://doi.org/10.1007/s00262-012-1284-7

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