A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene

Hiroki Torikai, Yoshiki Akatsuka, Mikinori Miyazaki, Edus H. Warren, Taku Oba, Kunio Tsujimura, Kazuo Motoyoshi, Yasuo Morishima, Yoshihisa Kodera, Kiyotaka Kuzushima, Toshitada Takahashi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)7046-7054
Number of pages9
JournalJournal of Immunology
Volume173
Issue number11
DOIs
Publication statusPublished - 01-12-2004

Fingerprint

HLA-A*33 antigen
Minor Histocompatibility Antigens
Histocompatibility
Open Reading Frames
Stem Cell Transplantation
losigame
Genes
T-Lymphocytes
Epitopes
Peripheral Blood Stem Cell Transplantation
Initiator Codon
5' Untranslated Regions
Y Chromosome
Transfection
Siblings
Blood Cells
Clone Cells
Tissue Donors
Amino Acids
Cell Line

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Torikai, Hiroki ; Akatsuka, Yoshiki ; Miyazaki, Mikinori ; Warren, Edus H. ; Oba, Taku ; Tsujimura, Kunio ; Motoyoshi, Kazuo ; Morishima, Yasuo ; Kodera, Yoshihisa ; Kuzushima, Kiyotaka ; Takahashi, Toshitada. / A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene. In: Journal of Immunology. 2004 ; Vol. 173, No. 11. pp. 7046-7054.
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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.",
author = "Hiroki Torikai and Yoshiki Akatsuka and Mikinori Miyazaki and Warren, {Edus H.} and Taku Oba and Kunio Tsujimura and Kazuo Motoyoshi and Yasuo Morishima and Yoshihisa Kodera and Kiyotaka Kuzushima and Toshitada Takahashi",
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Torikai, H, Akatsuka, Y, Miyazaki, M, Warren, EH, Oba, T, Tsujimura, K, Motoyoshi, K, Morishima, Y, Kodera, Y, Kuzushima, K & Takahashi, T 2004, 'A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene', Journal of Immunology, vol. 173, no. 11, pp. 7046-7054. https://doi.org/10.4049/jimmunol.173.11.7046

A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene. / Torikai, Hiroki; Akatsuka, Yoshiki; Miyazaki, Mikinori; Warren, Edus H.; Oba, Taku; Tsujimura, Kunio; Motoyoshi, Kazuo; Morishima, Yasuo; Kodera, Yoshihisa; Kuzushima, Kiyotaka; Takahashi, Toshitada.

In: Journal of Immunology, Vol. 173, No. 11, 01.12.2004, p. 7046-7054.

Research output: Contribution to journalArticle

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AU - Torikai, Hiroki

AU - Akatsuka, Yoshiki

AU - Miyazaki, Mikinori

AU - Warren, Edus H.

AU - Oba, Taku

AU - Tsujimura, Kunio

AU - Motoyoshi, Kazuo

AU - Morishima, Yasuo

AU - Kodera, Yoshihisa

AU - Kuzushima, Kiyotaka

AU - Takahashi, Toshitada

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