title: A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene.
abstract: Female-to-male hemopoietic stem cell transplantation (HSCT) elicits T cell responses against male-specific minor histocompatibility (H-Y) Ags encoded by the Y chromosome. All previously identified H-Y Ags are encoded by conventional open reading frames, but we report in this study the identification of a novel H-Y Ag encoded in the 5'-untranslated region of the TMSB4Y gene. An HLA-A*3303-restricted CD8(+) CTL clone was isolated from a male patient after an HSCT from his HLA-identical sister. Using a panel of cell lines carrying Y chromosome terminal deletions, a narrow region controlling the susceptibility of these target cells to CTL recognition was localized. Minigene transfection and epitope reconstitution assays identified an 11-mer peptide, EVLLRPGLHFR, designated TMSB4Y/A33, whose first amino acid was located 405 bp upstream of the TMSB4Y initiation codon. Analysis of the precursor frequency of CTL specific for recipient minor histocompatibility Ags in post-HSCT peripheral blood T cells revealed that a significant fraction of the total donor CTL response in this patient was directed against the TMSB4Y epitope. Tetramer analysis continued to detect TMSB4Y/A33-specific CD8(+) T cells at least up to 700 days post-HSCT. This finding underscores the in vivo immunological relevance of minor histocompatibility Ags derived from unconventional open reading frame products.
authors.affiliation: Division of Immunology, Aichi Cancer Center Research Institute, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Torikai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: Mikinori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Taku
authors.initials: T
authors.lastname: Oba
authors.forename: Kunio
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kuzushima
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006182:H-Y Antigen / Q000276:immunology / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000276:immunology*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D017384:Sequence Deletion / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology; D013947:Thymosin / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D000099201:Thymosin beta(4)
chemical_list: D020121:5' Untranslated Regions; D006182:H-Y Antigen; D015234:HLA-A Antigens; D015778:Minor Histocompatibility Antigens; D020033:Protein Isoforms; D012333:RNA, Messenger; D013947:Thymosin; D000099201:Thymosin beta(4); C082945:HLA-A*33 antigen