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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3286-3294. Prepublished online as a Blood First Edition Paper on January 4, 2008; DOI 10.1182/blood-2007-10-118950. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2007-10-118950v1 111/6/3286    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawase, T. Articles by Akatsuka, Y. Search for Related Content PubMed PubMed Citation Articles by Kawase, T. Articles by Akatsuka, Y. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA Takakazu Kawase1,2, Yasuhito Nannya35, Hiroki Torikai1, Go Yamamoto35, Makoto Onizuka6, Satoko Morishima1, Kunio Tsujimura7, Koichi Miyamura5,8, Yoshihisa Kodera5,8, Yasuo Morishima5,9, Toshitada Takahashi10, Kiyotaka Kuzushima1, Seishi Ogawa35, and Yoshiki Akatsuka1,5 1 Division of Immunology, 2 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; 3 Department of Hematology/Oncology and 4 21st Century COE Program, Graduate School of Medicine, University of Tokyo, Tokyo; 5 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama; 6 Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Isehara; 7 Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu; 8 Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya; 9 Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya; and 10 Aichi Comprehensive Health Science Center, Aichi Health Promotion Foundation, Chita-gun, Japan Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of antitumor effects and for graft-versus-host 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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