テラワキ セイゴウ   Seigo Terawaki
  寺脇 正剛
   所属   川崎医科大学  医学部 基礎医学 分子遺伝医学
   職種   特任講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function.
掲載誌名 正式名:International immunology
略  称:Int Immunol
ISSNコード:09538178/09538178
掲載区分国外
巻・号・頁 19(7),881-890頁
著者・共著者 Terawaki Seigo, Tanaka Yoshimasa, Nagakura Tomokazu, Hayashi Tamon, Shibayama Shiro, Muroi Kaori, Okazaki Taku, Mikami Bunzo, Garboczi David N, Honjo Tasuku, Minato Nagahiro
発行年月 2007/07
概要 The negative co-stimulatory receptor, programmed cell death 1 (PD-1), is induced on activated T cells and delivers inhibitory signals upon engagement with its ligands PD-L1 and PD-L2, which are expressed on various somatic cells and certain cancers. Accumulating evidence suggests that interfering with the PD-1-PD-L1 interaction may result in the restoration of defective T cell functions in cancer and chronic viral infection. Herein, we established procedures to produce large amounts of renatured recombinant extracellular domain proteins of mouse PD-1 (mPD-1) and PD-L1. While monomeric mPD-1 and mouse PD-L1 (mPD-L1) only marginally interacted with the cells expressing their counterpart proteins, their tetramerization markedly enhanced the affinity with the K(d) of mPD-L1 tetramer being nearly 100-fold lower than that of the corresponding monomer. The affinity of mPD-L1 tetramer was even higher than a high-affinity anti-PD-1 mAb, and it efficiently inhibited the binding of mPD-L1/Fc-chimeric protein to mPD-1(+) cells. Functionally, mPD-L1 tetramer significantly enhanced the proliferative responses as well as the cytotoxic activity of T cells against specific target cells in vitro. The results suggest that oligomeric PD-L1 extracellular domains may provide a potential means to restore T cell functions in cancer and viral infection in humans.
DOI 10.1093/intimm/dxm059
PMID 17606978