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

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41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3286-3294
Number of pages9
JournalBlood
Volume111
Issue number6
DOIs
Publication statusPublished - 15-03-2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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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, 111(6), 3286-3294. https://doi.org/10.1182/blood-2007-10-118950