Article abstract
Nature Immunology 8, 1001 - 1007 (2007)
Published online: 22 July 2007 | doi:10.1038/ni1492
Crystal structure of the IL-15–IL-15R
complex, a cytokine-receptor unit presented in trans
Mami Chirifu1,2, Chiharu Hayashi1,2, Teruya Nakamura1, Sachiko Toma1,3, Tsuyoshi Shuto1, Hirofumi Kai1, Yuriko Yamagata1, Simon J Davis4 & Shinji Ikemizu1,2
Abstract
Interleukin 15 (IL-15) and IL-2, which promote the survival of memory CD8+ T cells and regulatory T cells, respectively, bind receptor complexes that share 
- and 
-signaling subunits. Receptor specificity is provided by unique, nonsignaling 
-subunits. Whereas IL-2 receptor- (IL-2R) is expressed together in cis with the - and -subunits on T cells and B cells, IL-15R is expressed in trans on antigen-presenting cells. Here we present a 1.85-Å crystal structure of the human IL-15–IL-15R complex. The structure provides insight into the molecular basis of the specificity of cytokine recognition and emphasizes the importance of water in generating this very high-affinity complex. Despite very low IL-15–IL-2 sequence homology and distinct receptor architecture, the topologies of the IL-15–IL-15R and IL-2–IL-2R complexes are very similar. Our data raise the possibility that IL-2, like IL-15, might be capable of being presented in trans in the context of its unique receptor -chain.
- Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
- 21st Century Center of Excellence Project, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
- Graduate School of Sciences and Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033, Japan.
- Nuffield Department of Clinical Medicine, and Medical Research Council Human Immunology Unit, The University of Oxford, The Weatherall Institute of Molecular Medicine, Headington, Oxford, OX3 9DS, UK.
Correspondence to: Shinji Ikemizu1,2 e-mail: ikemizu@gpo.kumamoto-u.ac.jp
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