Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation

Jinsong Hu, Nana Dang, Hui Yao, Yu Li, Hongxin Zhang, Xiangmin Yang, Jing Xu, Huijie Bian, Jinliang Xing, Ping Zhu, Zhinan Chen

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

HAb18G/CD147, a glycoprotein of the immunoglobulin super-family (IgSF), is a T cell activation-associated molecule. In this report, we demonstrated that HAb18G/CD147 expression on both activated CD4+ and CD8+ T cells was up-regulated. In vitro cross-linking of T cells with an anti-HAb18G/CD147 monoclonal antibody (mAb) 5A12 inhibited T cells proliferation upon T cell receptor stimulation. Such co-stimulation inhibited T cell proliferation by down-regulating the expression of CD25 and interleukin-2 (IL-2), decreased production of IL-4 but not interferon-γ. Laser confocal imaging analysis indicated that HAb18G/CD147 was recruited to the immunological synapse (IS) during T cell activation; triggering HAb18G/CD147 on activated T cells by anti-HAb18G/CD147 mAb 5A12 strongly dispersed the formation of the IS. Further functional studies showed that the ligation of HAb18G/CD147 with mAb 5A12 decreased the tyrosine phosphorylation and intracellular calcium mobilization levels of T cells. Through docking antibody-antigen interactions, we demonstrated that the function of mAb 5A12 is tightly dependent on its specificity of binding to N-terminal domain I, which plays pivotal role in the oligomerization of HAb18G/CD147. Taken together, we provide evidence that HAb18G/CD147 could act as a co-stimulatory receptor to negatively regulate T cell activation and is functionally linked to the formation of the IS.

Original languageEnglish
Pages (from-to)2132-2143
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • Co-stimulatory molecule
  • HAb18G/CD147
  • IS
  • Lipid rafts
  • Molecular modelling and docking
  • T cell activation

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