Differential CD147 Functional Epitopes on Distinct Leukocyte Subsets

Abstract

CD147, a member of the immunoglobulin (Ig) superfamily, is widely expressed in several cell types. CD147 molecules have multiple cellular functions, such as migration, adhesion, invasion, energy metabolism and T cell activation. In particular, recent studies have demonstrated the potential application of CD147 as an effective therapeutic target for cancer, as well as autoimmune and inflammatory diseases. In this study, we elucidated the functional epitopes on CD147 extracellular domains in T cell regulation using specific monoclonal antibodies (mAbs). Upon T cell activation, the anti-CD147 domain 1 mAbs M6-1E9 and M6-1D4 and the anti-CD147 domain 2 mAb MEM-M6/6 significantly reduced surface expression of CD69 and CD25 and T cell proliferation. To investigate whether functional epitopes of CD147 are differentially expressed on distinct leukocyte subsets, PBMCs, monocyte-depleted PBMCs and purified T cells were activated in the presence of anti-CD147 mAbs. The mAb M6-1E9 inhibited T cell functions via activation of CD147 on monocytes with obligatory cell-cell contact. Engagement of the CD147 epitope by the M6-1E9 mAb downregulated CD80 and CD86 expression on monocytes and IL-2, TNF-α, IFN-γ and IL-17 production in T cells. In contrast, the mAb M6-1D4 inhibited T cell function via activation of CD147 on T cells by downregulating IL-2, TNF-α and IFN-γ. Herein, we demonstrated that certain epitopes of CD147, expressed on both monocytes and T cells, are involved in the regulation of T cell activation.

Neutralizing antibody and T cell responses against SARS-CoV-2 variants of concern following ChAdOx-1 or BNT162b2 boosting in the elderly previously immunized with CoronaVac vaccine

“…This discrepancy was not surprising and could be due to the methods and subjects of the different studies. The interferon-γ release assay (IGRA) was employed in previous studies, [ 24 , 56 ] while intracellular IFN-γ expression in CD4 and CD8 T cells [ 57 ] was evaluated in the present study. Through the intracellular cytokine assay, the numbers of IFN-γ-producing CD4 and CD8 T cells could be directly monitored upon stimulation with S peptide pools.…”

Single-cell RNA sequencing reveals Immune Education promotes T cell survival in mice subjected to the cecal ligation and puncture sepsis model

“…Hurdle analysis of quiescent naïve CD4 T cells identified 31 DEGs; following Immune Education and CLP versus CLP alone, expression in 24 was upregulated while expression in 7 was downregulated. Among the affected genes in the Immune-Educated CLP mice was Bsg (upregulated 2.29 fold, P <0.001), whose encoded protein basigin/CD147 has been shown to play a role in T cell activation and T reg differentiation, and because of this it has been studied as a potential therapeutic target for inflammatory diseases ( 82 , 83 ). There was also upregulation of Cdc42 (upregulated 2.25 fold, P <0.001), whose encoded protein (a Rho family GTPase) has been shown to play an essential role in actin polymerization for TCR clustering, Th1 differentiation, and memory cell survival in naïve CD4 T cells ( 84 ).…”

Differential immunophenotype of circulating monocytes from pregnant women in response to viral ligands

“…Herein, we showed that the frequency of monocytes expressing the adhesion molecules CD147 and CD162 was diminished in pregnant women in response to TLR7/TLR8 stimulation. CD147, commonly termed Basigin, is a membrane receptor and member of the immunoglobulin superfamily that participates in cellular functions including migration and adhesion [ 77 – 80 ]. Similarly, CD162, or P-selectin glycoprotein ligand-1 (PSGL-1), acts as a ligand for selectins and is also a key player in leukocyte migration/adhesion [ 81 – 83 ].…”