Crystal structure of the il-15–il-15rα complex, a cytokine-receptor unit presented in trans

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 β- and γ-signaling

subunits. Receptor specificity is provided by unique, nonsignaling α-subunits. Whereas IL-2 receptor-α (IL-2Rα) is expressed together _in cis_ with the β- and γ-subunits on T cells and B

cells, IL-15Rα is expressed _in trans_ on antigen-presenting cells. Here we present a 1.85-Å crystal structure of the human IL-15–IL-15Rα 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-15Rα and IL-2–IL-2Rα 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 α-chain. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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Supported by a Grant-in-Aid for Creative Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, the Uehara Memorial Foundation, the Natio Foundation,

the Astellas Foundation for Research on Metabolic Disorders, the Takeda Science Foundation, the Suzuken Memorial Foundation, the Kanae Foundation for the Promotion of Medical Science, the

Astellas Foundation for Research on Medicinal Resources, Japan Research Foundation for Clinical Pharmacology, and The Wellcome Trust. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Graduate

School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan Mami Chirifu, Chiharu Hayashi, Teruya Nakamura, Sachiko Toma, Tsuyoshi Shuto, Hirofumi Kai,

 Yuriko Yamagata & Shinji Ikemizu * 21st Century Center of Excellence Project, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan Mami Chirifu, Chiharu Hayashi & Shinji

Ikemizu * Graduate School of Sciences and Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan Sachiko Toma * Nuffield Department of Clinical

Medicine, and Medical Research Council Human Immunology Unit, The University of Oxford, The Weatherall Institute of Molecular Medicine, Headington, OX3 9DS, Oxford, UK Simon J Davis Authors

* Mami Chirifu View author publications You can also search for this author inPubMed Google Scholar * Chiharu Hayashi View author publications You can also search for this author inPubMed 

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author inPubMed Google Scholar * Tsuyoshi Shuto View author publications You can also search for this author inPubMed Google Scholar * Hirofumi Kai View author publications You can also

search for this author inPubMed Google Scholar * Yuriko Yamagata View author publications You can also search for this author inPubMed Google Scholar * Simon J Davis View author publications

You can also search for this author inPubMed Google Scholar * Shinji Ikemizu View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS M.C., C.H.,

T.N., S.T., T.S., H.K. and Y.Y. did the research; S.J.D. and S.I. designed experiments, interpreted data and prepared the manuscript; and S.I. conceived and supervised the project.

CORRESPONDING AUTHOR Correspondence to Shinji Ikemizu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY

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Crystal structure of the IL-15–IL-15Rα complex, a cytokine-receptor unit presented _in trans_. _Nat Immunol_ 8, 1001–1007 (2007). https://doi.org/10.1038/ni1492 Download citation * Received:

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