Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation
Jinsong Hu
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
These authors contributed equally to this study.
Search for more papers by this authorNana Dang
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, People’s Republic of China
These authors contributed equally to this study.
Search for more papers by this authorHui Yao
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
These authors contributed equally to this study.
Search for more papers by this authorYu Li
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
Search for more papers by this authorHongxin Zhang
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
Search for more papers by this authorXiangmin Yang
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
Search for more papers by this authorJing Xu
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
Search for more papers by this authorHuijie Bian
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
Search for more papers by this authorJinliang Xing
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
Search for more papers by this authorCorresponding Author
Ping Zhu
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China
Correspondence to: Zhinan CHEN, Ping ZHU,Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi’an 710032, People’s Republic of China.Tel.: 1186(29)84774547Fax: 1186(29)83226349E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Zhinan Chen
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
Correspondence to: Zhinan CHEN, Ping ZHU,Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi’an 710032, People’s Republic of China.Tel.: 1186(29)84774547Fax: 1186(29)83226349E-mail: [email protected], [email protected]Search for more papers by this authorJinsong Hu
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
These authors contributed equally to this study.
Search for more papers by this authorNana Dang
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, People’s Republic of China
These authors contributed equally to this study.
Search for more papers by this authorHui Yao
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
These authors contributed equally to this study.
Search for more papers by this authorYu Li
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
Search for more papers by this authorHongxin Zhang
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
Search for more papers by this authorXiangmin Yang
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
Search for more papers by this authorJing Xu
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
Search for more papers by this authorHuijie Bian
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
Search for more papers by this authorJinliang Xing
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
Search for more papers by this authorCorresponding Author
Ping Zhu
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China
Correspondence to: Zhinan CHEN, Ping ZHU,Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi’an 710032, People’s Republic of China.Tel.: 1186(29)84774547Fax: 1186(29)83226349E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Zhinan Chen
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
Correspondence to: Zhinan CHEN, Ping ZHU,Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi’an 710032, People’s Republic of China.Tel.: 1186(29)84774547Fax: 1186(29)83226349E-mail: [email protected], [email protected]Search for more papers by this authorAbstract
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.
Supporting Information
Fig. S1 G1 phase cell cycle arrest provoked in T cells by mAb 5A12. Cell cycle distribution was assessed by flow cytometry analysis of propidium iodide-stained nuclei. The data were representative of three independently performed experiments.
Fig. S2 Molecular modelling of anti-HAb18G/CD147 mAbs. (A) Cloning and sequencing the heavy chain Fd and full-length light chain genes of mAb HAb18, 5A12, 6H8. Shadowed sequences indicate the PCR primers. (B) The modelled 3D structure of anti-HAb18G/CD147 mAb HAb18, 5A12 and 6H8.
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