Dictating Phenotype, Function, and Fate of Human T Cells with Co‐Stimulatory Antibodies Presented by Filamentous Immune Cell Mimics

T cells require a co-stimulatory signal in addition to T-cell receptor (TCR) stimulation to achieve full activation. While most studies focus on the co-stimulatory receptor CD28, little is known about the role of the other co-stimulatory receptors in T-cell signaling. A deeper understanding of how co-stimulatory receptor signaling cooperates with TCR signaling could improve the ability to control T-cell function and benefit the design of T-cell based immunotherapies. Artificial antigen presenting cells (aAPCs) enable tight control over the signals given to T cells. In this study, filamentous polyisocyanopeptide (PIC) polymers (immunofilaments) are used as nanosized aAPCs to study the role of the engagement of six distinct co-stimulatory molecules on human T-cell phenotype, function, and fate in the context of TCR signaling. The immunofilaments highlight important roles for CD28 and CD2 signaling in T-cell priming, proliferation, cytokine production, and multifunctionality. Taken together, this work provides insight into the role of combined TCR and co-stimulation on T-cell phenotype, function, and fate using immunofilaments. Notably, the findings on the roles of co-stimulatory molecule function can be used for the rational design of future cancer immunotherapies.