The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303

H. Torikai, Yoshiki Akatsuka, M. Miyazaki, A. Tsujimura, Y. Yatabe, T. Kawase, Y. Nakao, K. Tsujimura, K. Motoyoshi, Y. Morishima, Y. Kodera, K. Kuzushima, T. Takahashi

研究成果: Article

23 引用 (Scopus)

抄録

Minor histocompatibility antigens (mHags) play crucial roles in the induction of graft versus host disease (GVHD) and/or graft versus leukaemia (GVL) effects following human leucocyte antigen (HLA)-identical haematopoietic stem cell transplantation (HSCT). Using HLA-A*3101- and -A*3303-restricted cytotoxic T lymphocyte (CTL) clones generated from different post-HSCT recipients, we identified two novel mHag epitopes encoded by the leader sequence of cathepsin H (CTSH) isoform a. The nonameric sequence ATLPLLCAR was defined as an HLA-A*3101-restricted epitope (CTSH R/A31), while a decameric peptide featuring a one N-terminal amino acid extension, WATLPLLCAR, was presented by HLA-A*3303 (CTSH R/A33). The immunogenicity of both epitopes was totally dependent on the polymorphic C-terminal arginine residue and substitution with glycine completely abolished binding to the corresponding HLA molecules. Thus, the immunogenicity of this mHag is exerted by differential HLA binding capacity. CTSH is relatively ubiquitously expressed at protein levels, thus it may be involved in GVHD and anti-leukaemic/ tumour responses. Interestingly, however, CTL clones predominantly lysed targets of haematopoietic cell origin, which could not be explained in terms of the immunoproteasome system. Although the mechanisms involved in the differential susceptibility remain to be determined, these data suggest that CTSH-encoded mHags could be targets for GVL effects.

元の言語English
ページ(範囲)406-416
ページ数11
ジャーナルBritish Journal of Haematology
134
発行部数4
DOI
出版物ステータスPublished - 01-08-2006
外部発表Yes

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Cathepsin H
Minor Histocompatibility Antigens
HLA Antigens
Epitopes
Genes
Hematopoietic Stem Cell Transplantation
Cytotoxic T-Lymphocytes
Graft vs Host Disease
Leukemia
Clone Cells
Transplants
losigame
Glycine
Arginine
Protein Isoforms
Amino Acids
Peptides

All Science Journal Classification (ASJC) codes

  • Hematology

これを引用

Torikai, H. ; Akatsuka, Yoshiki ; Miyazaki, M. ; Tsujimura, A. ; Yatabe, Y. ; Kawase, T. ; Nakao, Y. ; Tsujimura, K. ; Motoyoshi, K. ; Morishima, Y. ; Kodera, Y. ; Kuzushima, K. ; Takahashi, T. / The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303. :: British Journal of Haematology. 2006 ; 巻 134, 番号 4. pp. 406-416.
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title = "The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303",
abstract = "Minor histocompatibility antigens (mHags) play crucial roles in the induction of graft versus host disease (GVHD) and/or graft versus leukaemia (GVL) effects following human leucocyte antigen (HLA)-identical haematopoietic stem cell transplantation (HSCT). Using HLA-A*3101- and -A*3303-restricted cytotoxic T lymphocyte (CTL) clones generated from different post-HSCT recipients, we identified two novel mHag epitopes encoded by the leader sequence of cathepsin H (CTSH) isoform a. The nonameric sequence ATLPLLCAR was defined as an HLA-A*3101-restricted epitope (CTSH R/A31), while a decameric peptide featuring a one N-terminal amino acid extension, WATLPLLCAR, was presented by HLA-A*3303 (CTSH R/A33). The immunogenicity of both epitopes was totally dependent on the polymorphic C-terminal arginine residue and substitution with glycine completely abolished binding to the corresponding HLA molecules. Thus, the immunogenicity of this mHag is exerted by differential HLA binding capacity. CTSH is relatively ubiquitously expressed at protein levels, thus it may be involved in GVHD and anti-leukaemic/ tumour responses. Interestingly, however, CTL clones predominantly lysed targets of haematopoietic cell origin, which could not be explained in terms of the immunoproteasome system. Although the mechanisms involved in the differential susceptibility remain to be determined, these data suggest that CTSH-encoded mHags could be targets for GVL effects.",
author = "H. Torikai and Yoshiki Akatsuka and M. Miyazaki and A. Tsujimura and Y. Yatabe and T. Kawase and Y. Nakao and K. Tsujimura and K. Motoyoshi and Y. Morishima and Y. Kodera and K. Kuzushima and T. Takahashi",
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Torikai, H, Akatsuka, Y, Miyazaki, M, Tsujimura, A, Yatabe, Y, Kawase, T, Nakao, Y, Tsujimura, K, Motoyoshi, K, Morishima, Y, Kodera, Y, Kuzushima, K & Takahashi, T 2006, 'The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303', British Journal of Haematology, 巻. 134, 番号 4, pp. 406-416. https://doi.org/10.1111/j.1365-2141.2006.06205.x

The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303. / Torikai, H.; Akatsuka, Yoshiki; Miyazaki, M.; Tsujimura, A.; Yatabe, Y.; Kawase, T.; Nakao, Y.; Tsujimura, K.; Motoyoshi, K.; Morishima, Y.; Kodera, Y.; Kuzushima, K.; Takahashi, T.

:: British Journal of Haematology, 巻 134, 番号 4, 01.08.2006, p. 406-416.

研究成果: Article

TY - JOUR

T1 - The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303

AU - Torikai, H.

AU - Akatsuka, Yoshiki

AU - Miyazaki, M.

AU - Tsujimura, A.

AU - Yatabe, Y.

AU - Kawase, T.

AU - Nakao, Y.

AU - Tsujimura, K.

AU - Motoyoshi, K.

AU - Morishima, Y.

AU - Kodera, Y.

AU - Kuzushima, K.

AU - Takahashi, T.

PY - 2006/8/1

Y1 - 2006/8/1

N2 - Minor histocompatibility antigens (mHags) play crucial roles in the induction of graft versus host disease (GVHD) and/or graft versus leukaemia (GVL) effects following human leucocyte antigen (HLA)-identical haematopoietic stem cell transplantation (HSCT). Using HLA-A*3101- and -A*3303-restricted cytotoxic T lymphocyte (CTL) clones generated from different post-HSCT recipients, we identified two novel mHag epitopes encoded by the leader sequence of cathepsin H (CTSH) isoform a. The nonameric sequence ATLPLLCAR was defined as an HLA-A*3101-restricted epitope (CTSH R/A31), while a decameric peptide featuring a one N-terminal amino acid extension, WATLPLLCAR, was presented by HLA-A*3303 (CTSH R/A33). The immunogenicity of both epitopes was totally dependent on the polymorphic C-terminal arginine residue and substitution with glycine completely abolished binding to the corresponding HLA molecules. Thus, the immunogenicity of this mHag is exerted by differential HLA binding capacity. CTSH is relatively ubiquitously expressed at protein levels, thus it may be involved in GVHD and anti-leukaemic/ tumour responses. Interestingly, however, CTL clones predominantly lysed targets of haematopoietic cell origin, which could not be explained in terms of the immunoproteasome system. Although the mechanisms involved in the differential susceptibility remain to be determined, these data suggest that CTSH-encoded mHags could be targets for GVL effects.

AB - Minor histocompatibility antigens (mHags) play crucial roles in the induction of graft versus host disease (GVHD) and/or graft versus leukaemia (GVL) effects following human leucocyte antigen (HLA)-identical haematopoietic stem cell transplantation (HSCT). Using HLA-A*3101- and -A*3303-restricted cytotoxic T lymphocyte (CTL) clones generated from different post-HSCT recipients, we identified two novel mHag epitopes encoded by the leader sequence of cathepsin H (CTSH) isoform a. The nonameric sequence ATLPLLCAR was defined as an HLA-A*3101-restricted epitope (CTSH R/A31), while a decameric peptide featuring a one N-terminal amino acid extension, WATLPLLCAR, was presented by HLA-A*3303 (CTSH R/A33). The immunogenicity of both epitopes was totally dependent on the polymorphic C-terminal arginine residue and substitution with glycine completely abolished binding to the corresponding HLA molecules. Thus, the immunogenicity of this mHag is exerted by differential HLA binding capacity. CTSH is relatively ubiquitously expressed at protein levels, thus it may be involved in GVHD and anti-leukaemic/ tumour responses. Interestingly, however, CTL clones predominantly lysed targets of haematopoietic cell origin, which could not be explained in terms of the immunoproteasome system. Although the mechanisms involved in the differential susceptibility remain to be determined, these data suggest that CTSH-encoded mHags could be targets for GVL effects.

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