Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses

  1. Masaaki Hashiguchi*,
  2. Hiroko Kobori*,
  3. Patcharee Ritprajak*,
  4. Yosuke Kamimura*,
  5. Haruo Kozono†, and
  6. Miyuki Azuma*,‡
  1. *Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan; and
  2. †Division of Biosignaling, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan

  1. Edited by James P. Allison, Memorial Sloan-Kettering Cancer Center, New York, NY, and approved May 14, 2008 (received for review March 11, 2008)

Abstract

The B7 family member B7-H3 (CD276) plays important roles in immune responses. However, the function of B7-H3 remains controversial. We found that murine B7-H3 specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2). TLT-2 was expressed on CD8+ T cells constitutively and on activated CD4+ T cells. Stimulation with B7-H3 transfectants preferentially up-regulated the proliferation and IFN-γ production of CD8+ T cells. Transduction of TLT-2 into T cells resulted in enhanced IL-2 and IFN-γ production via interactions with B7-H3. Blockade of the B7-H3:TLT-2 pathway with a mAb against B7-H3 or TLT-2 efficiently inhibited contact hypersensitivity responses. Our results demonstrate a direct interaction between B7-H3 and TLT-2 that preferentially enhances CD8+ T cell activation.

Footnotes

  • ‡To whom correspondence should be addressed. E-mail: miyuki.mim{at}tmd.ac.jp

  • Author contributions: M.H. and M.A. designed research; M.H., H. Kobori, P.R., Y.K., and H. Kozono performed research; M.H. and M.A. analyzed data; and M.H. and M.A. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • See Commentary on page 10277.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0802423105/DCSupplemental.

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  1. Published online before print July 23, 2008, doi: 10.1073/pnas.0802423105 PNAS July 29, 2008 vol. 105 no. 30 10495-10500
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