Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA

Takakazu Kawase, Yasuhito Nannya, Hiroki Torikai, Go Yamamoto, Makoto Onizuka, Satoko Morishima, Kunio Tsujimura, Koichi Miyamura, Yoshihisa Kodera, Yasuo Morishima, Toshitada Takahashi, Kiyotaka Kuzushima, Seishi Ogawa, Yoshiki Akatsuka

研究成果: Article

38 引用 (Scopus)

抄録

Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of antitumor effects and for graft-versushost disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, despite their potential clinical use, our knowledge of human minor H antigens is largely limited by the lack of efficient methods of their characterization. Here we report a robust and efficient method of minor H gene discovery that combines whole genome association scans (WGASs) with cytotoxic T-lymphocyte (CTL) assays, in which the genetic loci of minor H genes recognized by the CTL clones are precisely identified using pooled-DNA analysis of immortalized lymphoblastoid cell lines with/without susceptibility to those CTLs. Using this method, we have successfully mapped 2 loci: one previously characterized (HMSD encoding ACC-6), and one novel. The novel minor H antigen encoded by BCL2A1 was identified within a 26 kb linkage disequilibrium block on chromosome 15q25. which had been directly mapped by WGAS. The pool size required to identify these regions was no more than 100 individuals. Thus, once CTL clones are generated, this method should substantially facilitate discovery of minor H antigens applicable to targeted allo-immune therapies and also contribute to our understanding of human allo-immunity.

元の言語English
ページ(範囲)3286-3294
ページ数9
ジャーナルBlood
111
発行部数6
DOI
出版物ステータスPublished - 15-03-2008

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Minor Histocompatibility Antigens
Forensic Anthropology
T-cells
Cytotoxic T-Lymphocytes
Genes
Association reactions
DNA
Immunity
Clone Cells
Genome
Genetic Loci
Hematopoietic Stem Cell Transplantation
Linkage Disequilibrium
Genetic Association Studies
Chromosomes
Stem cells
Grafts
Assays
Cells
Transplants

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

これを引用

Kawase, T., Nannya, Y., Torikai, H., Yamamoto, G., Onizuka, M., Morishima, S., ... Akatsuka, Y. (2008). Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. Blood, 111(6), 3286-3294. https://doi.org/10.1182/blood-2007-10-118950
Kawase, Takakazu ; Nannya, Yasuhito ; Torikai, Hiroki ; Yamamoto, Go ; Onizuka, Makoto ; Morishima, Satoko ; Tsujimura, Kunio ; Miyamura, Koichi ; Kodera, Yoshihisa ; Morishima, Yasuo ; Takahashi, Toshitada ; Kuzushima, Kiyotaka ; Ogawa, Seishi ; Akatsuka, Yoshiki. / Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. :: Blood. 2008 ; 巻 111, 番号 6. pp. 3286-3294.
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abstract = "Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of antitumor effects and for graft-versushost disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, despite their potential clinical use, our knowledge of human minor H antigens is largely limited by the lack of efficient methods of their characterization. Here we report a robust and efficient method of minor H gene discovery that combines whole genome association scans (WGASs) with cytotoxic T-lymphocyte (CTL) assays, in which the genetic loci of minor H genes recognized by the CTL clones are precisely identified using pooled-DNA analysis of immortalized lymphoblastoid cell lines with/without susceptibility to those CTLs. Using this method, we have successfully mapped 2 loci: one previously characterized (HMSD encoding ACC-6), and one novel. The novel minor H antigen encoded by BCL2A1 was identified within a 26 kb linkage disequilibrium block on chromosome 15q25. which had been directly mapped by WGAS. The pool size required to identify these regions was no more than 100 individuals. Thus, once CTL clones are generated, this method should substantially facilitate discovery of minor H antigens applicable to targeted allo-immune therapies and also contribute to our understanding of human allo-immunity.",
author = "Takakazu Kawase and Yasuhito Nannya and Hiroki Torikai and Go Yamamoto and Makoto Onizuka and Satoko Morishima and Kunio Tsujimura and Koichi Miyamura and Yoshihisa Kodera and Yasuo Morishima and Toshitada Takahashi and Kiyotaka Kuzushima and Seishi Ogawa and Yoshiki Akatsuka",
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Kawase, T, Nannya, Y, Torikai, H, Yamamoto, G, Onizuka, M, Morishima, S, Tsujimura, K, Miyamura, K, Kodera, Y, Morishima, Y, Takahashi, T, Kuzushima, K, Ogawa, S & Akatsuka, Y 2008, 'Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA', Blood, 巻. 111, 番号 6, pp. 3286-3294. https://doi.org/10.1182/blood-2007-10-118950

Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. / Kawase, Takakazu; Nannya, Yasuhito; Torikai, Hiroki; Yamamoto, Go; Onizuka, Makoto; Morishima, Satoko; Tsujimura, Kunio; Miyamura, Koichi; Kodera, Yoshihisa; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka; Ogawa, Seishi; Akatsuka, Yoshiki.

:: Blood, 巻 111, 番号 6, 15.03.2008, p. 3286-3294.

研究成果: Article

TY - JOUR

T1 - Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA

AU - Kawase, Takakazu

AU - Nannya, Yasuhito

AU - Torikai, Hiroki

AU - Yamamoto, Go

AU - Onizuka, Makoto

AU - Morishima, Satoko

AU - Tsujimura, Kunio

AU - Miyamura, Koichi

AU - Kodera, Yoshihisa

AU - Morishima, Yasuo

AU - Takahashi, Toshitada

AU - Kuzushima, Kiyotaka

AU - Ogawa, Seishi

AU - Akatsuka, Yoshiki

PY - 2008/3/15

Y1 - 2008/3/15

N2 - Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of antitumor effects and for graft-versushost disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, despite their potential clinical use, our knowledge of human minor H antigens is largely limited by the lack of efficient methods of their characterization. Here we report a robust and efficient method of minor H gene discovery that combines whole genome association scans (WGASs) with cytotoxic T-lymphocyte (CTL) assays, in which the genetic loci of minor H genes recognized by the CTL clones are precisely identified using pooled-DNA analysis of immortalized lymphoblastoid cell lines with/without susceptibility to those CTLs. Using this method, we have successfully mapped 2 loci: one previously characterized (HMSD encoding ACC-6), and one novel. The novel minor H antigen encoded by BCL2A1 was identified within a 26 kb linkage disequilibrium block on chromosome 15q25. which had been directly mapped by WGAS. The pool size required to identify these regions was no more than 100 individuals. Thus, once CTL clones are generated, this method should substantially facilitate discovery of minor H antigens applicable to targeted allo-immune therapies and also contribute to our understanding of human allo-immunity.

AB - Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of antitumor effects and for graft-versushost disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, despite their potential clinical use, our knowledge of human minor H antigens is largely limited by the lack of efficient methods of their characterization. Here we report a robust and efficient method of minor H gene discovery that combines whole genome association scans (WGASs) with cytotoxic T-lymphocyte (CTL) assays, in which the genetic loci of minor H genes recognized by the CTL clones are precisely identified using pooled-DNA analysis of immortalized lymphoblastoid cell lines with/without susceptibility to those CTLs. Using this method, we have successfully mapped 2 loci: one previously characterized (HMSD encoding ACC-6), and one novel. The novel minor H antigen encoded by BCL2A1 was identified within a 26 kb linkage disequilibrium block on chromosome 15q25. which had been directly mapped by WGAS. The pool size required to identify these regions was no more than 100 individuals. Thus, once CTL clones are generated, this method should substantially facilitate discovery of minor H antigens applicable to targeted allo-immune therapies and also contribute to our understanding of human allo-immunity.

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