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.
authors.affiliation: Division of Immunology, Aichi Cancer Centre Research Institute, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Torikai
authors.forename: Y
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: A
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Y
authors.initials: Y
authors.lastname: Yatabe
authors.forename: T
authors.initials: T
authors.lastname: Kawase
authors.forename: Y
authors.initials: Y
authors.lastname: Nakao
authors.forename: K
authors.initials: K
authors.lastname: Tsujimura
authors.forename: K
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Morishima
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: K
authors.initials: K
authors.lastname: Kuzushima
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D056655:Cathepsin H; D002403:Cathepsins / Q000235:genetics*; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000235:genetics*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D008912:Minor Histocompatibility Loci / Q000276:immunology*; D008969:Molecular Sequence Data; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D020033:Protein Isoforms; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534126:CTSH protein, human; D056655:Cathepsin H