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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 (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 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 HighWire 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 22, 2007 Accepted December 19, 2007 Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA Takakazu Kawase, Yasuhito Nanya, Hiroki Torikai, Go Yamamoto, Makoto Onizuka, Satoko Morishima, Kunio Tsujimura, Koichi Miyamura, Yoshihisa Kodera, Yasuo Morishima, Toshitada Takahashi, Kiyotaka Kuzushima, Seishi Ogawa, and Yoshiki Akatsuka* Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan Departments of Hematology/Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan The 21st century COE Program, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Isehara, Japan Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Saitama, Japan Division of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan Aichi Comprehensive Health Science Center, Aichi Health Promotion Foundation, Chita-gun, Japan * Corresponding author; email: yakatsuk{at}aichi-cc.jp. Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of anti-tumor 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 (WGAS) 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 two loci: one previously characterized (HMSD encoding ACC-6), and one novel. The novel minor H antigen encoded by the 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? This article has been cited by other articles: R. M. Spaapen, R. A.L. de Kort, K. van den Oudenalder, M. van Elk, A. C. Bloem, H. M. Lokhorst, and T. Mutis Rapid Identification of Clinical Relevant Minor Histocompatibility Antigens via Genome-Wide Zygosity-Genotype Correlation Analysis Clin. Cancer Res., December 1, 2009; 15(23): 7137 - 7143. [Abstract] [Full Text] [PDF] A. N. Stumpf, E. D. van der Meijden, C. A. M. van Bergen, R. Willemze, J. H. F. Falkenburg, and M. Griffioen Identification of 4 new HLA-DR-restricted minor histocompatibility antigens as hematopoietic targets in antitumor immunity Blood, October 22, 2009; 114(17): 3684 - 3692. [Abstract] [Full Text] [PDF] M. Kamei, Y. Nannya, H. Torikai, T. Kawase, K. Taura, Y. Inamoto, T. Takahashi, M. Yazaki, S. Morishima, K. Tsujimura, et al. HapMap scanning of novel human minor histocompatibility antigens Blood, May 21, 2009; 113(21): 5041 - 5048. [Abstract] [Full Text] [PDF] R. M. Spaapen, H. M. Lokhorst, K. van den Oudenalder, B. E. Otterud, H. Dolstra, M. F. Leppert, M. C. Minnema, A. C. Bloem, and T. Mutis Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel genome-wide analysis J. Exp. Med., November 24, 2008; 205(12): 2863 - 2872. [Abstract] [Full Text] [PDF]

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