As the complexity of biotechnology increases, the ability to control the interaction between cells and biomaterials is garnering the interest of an increasing audience. Cells contact artificial surfaces in a broad range of essential applications including medical implants and in vitro cell culture, to name a few. The projects in this thesis focused on creating and engineering three different biomaterials to interact with a model cell, the thymus lymphocyte (T cell), in a controllable manner. The first data chapter illustrates the fabrication and subsequent testing of a nanoparticle-protein conjugate with the ultimate goal of better understanding the binding interaction of the T cell receptor and its cognate ligand. The second chapter involves the creation of micropatterned, antigen-presenting cells that were meant to act as a biomaterials-based vaccine by interacting with and activating T cells. Finally, the fourth chapter describes a novel chemically degradable hydrogel system and the proof-of-concept experiments performed to encapsulate T cells. Interestingly, each of these projects features biomaterials that are representative of different size-regimes - nano, micro, and macro(millimeter). While the materials are different in size, they share the common goal of controllably interacting with T cells and use some of the same basic concepts and methods to reach this goal.