Crosslinking CD81 results in activation of TCRγδ T cells

CD81 is expressed on most cells and is associated with other glycoproteins, including CD4 and CD8, to form multimolecular membrane complexes. Crosslinking of CD81 on TCRαβ⁺ T cells results in costimulatory signals that have been proposed to be mediated via CD4 or CD8. In this study, we show that CD81 is also expressed on TCRγδ⁺CD4^-CD8^- T cells. CD81 crosslinking greatly enhanced anti-CD3 activation of both TCRαβ⁺ (CD4⁺ and CD8⁺) and TCRγδ⁺ T cells with regard to IFN-γ production. However, crosslinking of CD81 molecules on TCRγδ⁺ T cells, in the absence of anti-CD3 stimulation, resulted in cytokine production and enhanced IL-2-induced proliferation, demonstrating that physical association with CD4 or CD8 is not necessary for CD81 signaling. In contrast, crosslinking of CD81 on TCRαβ⁺ T cells, in the absence of anti-CD3 stimulation, failed to activate these T cells. These results suggest that CD81 signaling may be mediated via a different mechanism(s) in TCRγδ⁺ versus TCRαβ⁺ T cells.