Seigo Terawaki
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,
   Position   Assistant Professor with Special Assignment
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 / ForeginForegin
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