HapMap scanning of novel human minor histocompatibility antigens

Michi Kamei, Yasuhito Nannya, Hiroki Torikai, Takakazu Kawase, Kenjiro Taura, Yoshihiro Inamoto, Taro Takahashi, Makoto Yazaki, Satoko Morishima, Kunio Tsujimura, Koichi Miyamura, Tetsuya Ito, Hajime Togari, Stanley R. Riddell, Yoshihisa Kodera, Yasuo Morishima, Toshitada Takahashi, Kiyotaka Kuzushima, Seishi Ogawa, Yoshiki Akatsuka

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Minor histocompatibility antigens (mHags) are molecular targets of alloimmunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.

Original languageEnglish
Pages (from-to)5041-5048
Number of pages8
JournalBlood
Volume113
Issue number21
DOIs
Publication statusPublished - 18-11-2009

Fingerprint

Minor Histocompatibility Antigens
HapMap Project
Scanning
Transplantation (surgical)
Hematopoietic Stem Cell Transplantation
Stem cells
T-cells
Graft vs Host Disease
Grafts
Medicine
Single Nucleotide Polymorphism
Assays
Genes
Transplantation
Tissue Donors
Association reactions
Genome
Prospective Studies
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kamei, M., Nannya, Y., Torikai, H., Kawase, T., Taura, K., Inamoto, Y., ... Akatsuka, Y. (2009). HapMap scanning of novel human minor histocompatibility antigens. Blood, 113(21), 5041-5048. https://doi.org/10.1182/blood-2008-07-171678
Kamei, Michi ; Nannya, Yasuhito ; Torikai, Hiroki ; Kawase, Takakazu ; Taura, Kenjiro ; Inamoto, Yoshihiro ; Takahashi, Taro ; Yazaki, Makoto ; Morishima, Satoko ; Tsujimura, Kunio ; Miyamura, Koichi ; Ito, Tetsuya ; Togari, Hajime ; Riddell, Stanley R. ; Kodera, Yoshihisa ; Morishima, Yasuo ; Takahashi, Toshitada ; Kuzushima, Kiyotaka ; Ogawa, Seishi ; Akatsuka, Yoshiki. / HapMap scanning of novel human minor histocompatibility antigens. In: Blood. 2009 ; Vol. 113, No. 21. pp. 5041-5048.
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Kamei, M, Nannya, Y, Torikai, H, Kawase, T, Taura, K, Inamoto, Y, Takahashi, T, Yazaki, M, Morishima, S, Tsujimura, K, Miyamura, K, Ito, T, Togari, H, Riddell, SR, Kodera, Y, Morishima, Y, Takahashi, T, Kuzushima, K, Ogawa, S & Akatsuka, Y 2009, 'HapMap scanning of novel human minor histocompatibility antigens', Blood, vol. 113, no. 21, pp. 5041-5048. https://doi.org/10.1182/blood-2008-07-171678

HapMap scanning of novel human minor histocompatibility antigens. / Kamei, Michi; Nannya, Yasuhito; Torikai, Hiroki; Kawase, Takakazu; Taura, Kenjiro; Inamoto, Yoshihiro; Takahashi, Taro; Yazaki, Makoto; Morishima, Satoko; Tsujimura, Kunio; Miyamura, Koichi; Ito, Tetsuya; Togari, Hajime; Riddell, Stanley R.; Kodera, Yoshihisa; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka; Ogawa, Seishi; Akatsuka, Yoshiki.

In: Blood, Vol. 113, No. 21, 18.11.2009, p. 5041-5048.

Research output: Contribution to journalArticle

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T1 - HapMap scanning of novel human minor histocompatibility antigens

AU - Kamei, Michi

AU - Nannya, Yasuhito

AU - Torikai, Hiroki

AU - Kawase, Takakazu

AU - Taura, Kenjiro

AU - Inamoto, Yoshihiro

AU - Takahashi, Taro

AU - Yazaki, Makoto

AU - Morishima, Satoko

AU - Tsujimura, Kunio

AU - Miyamura, Koichi

AU - Ito, Tetsuya

AU - Togari, Hajime

AU - Riddell, Stanley R.

AU - Kodera, Yoshihisa

AU - Morishima, Yasuo

AU - Takahashi, Toshitada

AU - Kuzushima, Kiyotaka

AU - Ogawa, Seishi

AU - Akatsuka, Yoshiki

PY - 2009/11/18

Y1 - 2009/11/18

N2 - Minor histocompatibility antigens (mHags) are molecular targets of alloimmunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.

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Kamei M, Nannya Y, Torikai H, Kawase T, Taura K, Inamoto Y et al. HapMap scanning of novel human minor histocompatibility antigens. Blood. 2009 Nov 18;113(21):5041-5048. https://doi.org/10.1182/blood-2008-07-171678