Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2 (original) (raw)

Nature volume 419, pages 629–633 (2002)Cite this article

Abstract

Semaphorins are a family of phylogenetically conserved soluble and transmembrane proteins1,2. Although many soluble semaphorins deliver guidance cues to migrating axons during neuronal development3,4,5, some members are involved in immune responses6,7,8,9. For example, CD100 (also known as Sema4D), a class IV transmembrane semaphorin, signals through CD72 to effect nonredundant roles in immune responses7,10,11,12,13 in a ligand–receptor system that is distinct from any seen previously in the nervous system14,15. Here we report that the class IV semaphorin Sema4A, which is expressed in dendritic cells and B cells, enhances the in vitro activation and differentiation of T cells and the in vivo generation of antigen-specific T cells. Treating mice with monoclonal antibodies against Sema4A blocks the development of an experimental autoimmune encephalomyelitis that is induced by an antigenic peptide derived from myelin oligodendrocyte glycoprotein. In addition, expression cloning shows that the Sema4A receptor is Tim-2, a member of the family of T-cell immunoglobulin domain and mucin domain (Tim) proteins that is expressed on activated T cells.

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Acknowledgements

We thank K. Kubota for secretarial assistance; E. L. Barsoumian for critically reading the manuscript; and K. Nakamura, K. Shiozaki, S. Koga and J. Fujikake for technical support. This study was supported by research grants from the Ministry of Education, Culture, Science and Technology of Japan to H.K. and A.K.

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Author notes

  1. Atsushi Kumanogoh, Satoko Marukawa, Kazuhiro Suzuki, Harutoshi Fujimura and Saburo Sakoda: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, 565-0871, Osaka, Japan
    Atsushi Kumanogoh, Satoko Marukawa, Kazuhiro Suzuki, Noriko Takegahara, Chie Watanabe, EweSeng Ch'ng, Isao Ishida, Kanji Yoshida & Hitoshi Kikutani
  2. Department of Internal Medicine and Molecular Science, Osaka University, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan
    Satoko Marukawa
  3. Department of Neurology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan
    Harutoshi Fujimura & Saburo Sakoda

Authors

  1. Atsushi Kumanogoh
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  2. Satoko Marukawa
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  3. Kazuhiro Suzuki
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  4. Noriko Takegahara
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  5. Chie Watanabe
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  6. EweSeng Ch'ng
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  7. Isao Ishida
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  8. Harutoshi Fujimura
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  9. Saburo Sakoda
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  10. Kanji Yoshida
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  11. Hitoshi Kikutani
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Correspondence toHitoshi Kikutani.

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Kumanogoh, A., Marukawa, S., Suzuki, K. et al. Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2.Nature 419, 629–633 (2002). https://doi.org/10.1038/nature01037

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