Seigo Terawaki
Department Kawasaki Medical School Kawasaki Medical School, Department of Molecular and Genetic Medicine, Position Assistant Professor with Special Assignment |
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Article types | 原著 |
Language | English |
Peer review | Peer reviewed |
Title | Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function. |
Journal | Formal name:International immunology Abbreviation:Int Immunol ISSN code:09538178/09538178 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 19(7),pp.881-890 |
Author and coauthor | Terawaki Seigo, Tanaka Yoshimasa, Nagakura Tomokazu, Hayashi Tamon, Shibayama Shiro, Muroi Kaori, Okazaki Taku, Mikami Bunzo, Garboczi David N, Honjo Tasuku, Minato Nagahiro |
Authorship | Lead author |
Publication date | 2007/07 |
Summary | 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 |