Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs

E. Yamada, A. Demachi-Okamura, S. Kondo, Yoshiki Akatsuka, S. Suzuki, K. Shibata, F. Kikkawa, Kiyotaka Kuzushima

Research output: Contribution to journalArticle

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Abstract

Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T-lymphocyte (CTL) clone, 1G3, established from naïve CD8+ T-lymphocytes obtained from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive T-cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T-cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.

Original languageEnglish
Pages (from-to)164-171
Number of pages8
JournalTissue Antigens
Volume86
Issue number3
DOIs
Publication statusPublished - 01-09-2015

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HLA Antigens
Ovarian Neoplasms
Peptides
T-Lymphocytes
Clone Cells
RNA-Binding Proteins
Cytotoxic T-Lymphocytes
T-Cell Antigen Receptor
Gene Library
Epitopes
Complementary DNA
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

Cite this

Yamada, E., Demachi-Okamura, A., Kondo, S., Akatsuka, Y., Suzuki, S., Shibata, K., ... Kuzushima, K. (2015). Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs. Tissue Antigens, 86(3), 164-171. https://doi.org/10.1111/tan.12607
Yamada, E. ; Demachi-Okamura, A. ; Kondo, S. ; Akatsuka, Yoshiki ; Suzuki, S. ; Shibata, K. ; Kikkawa, F. ; Kuzushima, Kiyotaka. / Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs. In: Tissue Antigens. 2015 ; Vol. 86, No. 3. pp. 164-171.
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Yamada, E, Demachi-Okamura, A, Kondo, S, Akatsuka, Y, Suzuki, S, Shibata, K, Kikkawa, F & Kuzushima, K 2015, 'Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs', Tissue Antigens, vol. 86, no. 3, pp. 164-171. https://doi.org/10.1111/tan.12607

Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs. / Yamada, E.; Demachi-Okamura, A.; Kondo, S.; Akatsuka, Yoshiki; Suzuki, S.; Shibata, K.; Kikkawa, F.; Kuzushima, Kiyotaka.

In: Tissue Antigens, Vol. 86, No. 3, 01.09.2015, p. 164-171.

Research output: Contribution to journalArticle

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T1 - Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs

AU - Yamada, E.

AU - Demachi-Okamura, A.

AU - Kondo, S.

AU - Akatsuka, Yoshiki

AU - Suzuki, S.

AU - Shibata, K.

AU - Kikkawa, F.

AU - Kuzushima, Kiyotaka

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N2 - Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T-lymphocyte (CTL) clone, 1G3, established from naïve CD8+ T-lymphocytes obtained from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive T-cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T-cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.

AB - Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T-lymphocyte (CTL) clone, 1G3, established from naïve CD8+ T-lymphocytes obtained from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive T-cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T-cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.

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