Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation.
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.
Hu
Jinsong
J
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.
Dang
Nana
N
Yao
Hui
H
Li
Yu
Y
Zhang
Hongxin
H
Yang
Xiangmin
X
Xu
Jing
J
Bian
Huijie
H
Xing
Jinliang
J
Zhu
Ping
P
Chen
Zhinan
Z
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D051926:Basigin / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000378:metabolism; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; C497886:BSG protein, human; D016207:Cytokines; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D051926:Basigin; D014443:Tyrosine; D002118:Calcium