Programmable Anti-CD3 Oligomers Architectures to Decode and Control TCR Clustering Background and Rationale T-cell activation is initiated when the T-cell receptor (TCR) and associated CD3 complex form nanoscale clusters at the cell membrane. Although anti-CD3 antibodies are widely used to activate T cells and redirect them in cancer therapy, conventional antibodies poorly control cluster size, geometry, spacing, and signaling strength because they are large, bivalent, and structurally inflexible. Nanobodies (VHHs) or scFvs offer a strong alternative. This project uses anti-CD3 nanobodies as programmable building blocks to precisely control TCR clustering and define how receptor geometry determines T-cell activation.