Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation |
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Authors: | Jinsong Hu Nana Dang Hui Yao Yu Li Hongxin Zhang Xiangmin Yang Jing Xu Huijie Bian Jinliang Xing Ping Zhu Zhinan Chen |
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Institution: | 1. State Key Laboratory of Cancer Biology, Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi’an, People’s Republic of China;2. These authors contributed equally to this study.;3. State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, People’s Republic of China;4. Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China |
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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. |
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Keywords: | HAb18G/CD147 T cell activation co‐stimulatory molecule lipid rafts IS molecular modelling and docking |
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