Involvement of HAb18G/CD147 in T cell activation and immunological synapse formation.
Bottom Line: HAb18G/CD147, a glycoprotein of the immunoglobulin super-family (IgSF), is a T cell activation-associated molecule.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.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.
Affiliation: 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.Show MeSH
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Mentions: The sequences of the heavy chain Fd fragment and light chain of HAb18, 5A12 and 6H8 were cloned and analysed (Fig. S2). We found that the variable regions (Fv) of the three anti-HAb18G/CD147 mAbs are different. By using computer-assisted molecular modelling and docking, the interactions of HAb18G/CD147 epitope antigen with specific anti-HAb18G/CD147 mAbs were examined. It was found that these three mAbs, HAb18, 5A12 and 6H8 have different conformations, and recognize different regions of HAb18G/CD147 (Fig. 8). Among these three mAbs, HAb18 binds with N-terminal of HAb18G/CD147 in the manner of head to head, 5A12 and 6H8 were typically docked to the N-terminal IgC2 domain I (amino acid residues 22–101) and C-terminal IgI domain I (amino acid residues 107–205), respectively. At the docked conformation, a number of amino acid residues of HAb18G/CD147 critical to the interactions were identified and listed as follows: (1) HAb18: Glu39, Thr51, Asp65; (2) 6H8: Ser145, Arg184, Asp194 and (3) 5A12: Thr25, Asp32, Glu84, Thr96, Gln100.
Affiliation: 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.