Selective Activation of Antigen-Specific T Cells by Anti-CD3 Constraining Nano-particles (58.15)

Abstract

Upon antigen (Ag) recognition, TCRs form nanoscale clusters on the T cell surface. We hypothesized that the spatial differences of surface TCR between naïve and previously activated cells might be exploited by using anti-CD3 coated quantum dots (Qdots) to selectively activate Ag-specific cells. Rag-/- Pigeon Cytochrome c (PCC) specific CD4+ T cells were activated with APC +/- PCC with or without anti-CD3 Qdots. Anti-CD3 Qdots markedly enhanced proliferation of T cells incubated with low dose PCC but did not drive proliferation of T cells incubated with APC alone, though such cells proliferated to soluble anti-CD3. Additionally, anti-CD3 Qdots increased cytokine production of such cells in TH1 and TH2 cultures. We also explored the effect of anti-CD3 Qdots on heterogeneous cultures containing Rag+/+ hemagglutinin peptide (HA) specific 6.5+ CD4+ T cells and bystander 6.5- CD4+ T cells. Soluble anti-CD3 resulted in proliferation of both 6.5+ and 6.5- T cells. Cultures including low dose HA induced only 6.5+ T cells to proliferate, and addition of anti-CD3 Qdots further selectively enhanced proliferation of 6.5+ T cells but not 6.5- T cells in the same culture. This effect was again seen using CD8+ TCR transgenic T cells specific for class I HA. In vivo, anti-CD3 Qdots also increased the recovery of 6.5+ cells in a 6.5 adoptive transfer and HA vaccination model. Thus, constraining anti-CD3 on a nanoparticle confers an Ag-specific “nano boost” to T cell proliferation and function.