Selective activation of antigen-experienced T cells by anti-CD3 constrained on nanoparticles

Activation of T cells through the TCR is mediated by the TCR-CD3 signaling complex. Cross linking of this complex with Abs directed against CD3 leads to potent activation of T cells. However, such activation is not Ag-specific. We exploited the observation that the TCR-CD3 complex is clustered on T cells that have been activated by Ag by using anti-CD3 nanoparticles to selectively activate Ag-experienced mouse T cells. We find that constraining anti-CD3 on the surface of a nanoparticle markedly and selectively enhances proliferation and cytokine production of Ag-experienced T cells but does not activate naive T cells. This effect was recapitulated in heterogeneous cultures containing mixtures of Ag-specific CD4⁺ or CD8⁺ T cells and bystander T cells. Furthermore, in vivo anti-CD3-coated nanoparticles increased the expansion of Ag-specific T cells following vaccination. Overall, these findings indicate that anti-CD3-coated nanoparticles could be use to enhance the efficacy of vaccines and immunotherapy. The results also suggest constraining a ligand on the surface of a nanoparticle might as general strategy for selectively targeting clustered receptors.