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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)406-416
Number of pages11
JournalBritish Journal of Haematology
Volume134
Issue number4
DOIs
Publication statusPublished - 01-08-2006
Externally publishedYes

Fingerprint

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

Cite this

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. In: British Journal of Haematology. 2006 ; Vol. 134, No. 4. pp. 406-416.
@article{cc2290bb254f4931a847339db7529292,
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",
year = "2006",
month = "8",
day = "1",
doi = "10.1111/j.1365-2141.2006.06205.x",
language = "English",
volume = "134",
pages = "406--416",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "4",

}

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, vol. 134, no. 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.

In: British Journal of Haematology, Vol. 134, No. 4, 01.08.2006, p. 406-416.

Research output: Contribution to journalArticle

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.

UR - http://www.scopus.com/inward/record.url?scp=33746098876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746098876&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2006.06205.x

DO - 10.1111/j.1365-2141.2006.06205.x

M3 - Article

C2 - 16822283

AN - SCOPUS:33746098876

VL - 134

SP - 406

EP - 416

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 4

ER -