Defining the parameters necessary for T-cell recognition of ligands that vary in potency

Identification of the mechanisms by which a T cell is able to sense ligands of varying strength, such as those that mediate tumor growth, viral evasion, and autoimmunity, is a major goal of T-cell activation studies. In recent years, parameters important for T-cell activation by strong ligands (agonists) are beginning to be characterized. Here, we review our current work on the factors that are critical for T-cell activation by ligands that differ in potency, typified by full agonists, weak agonists, partial agonists, and antagonists. Furthermore, we discuss mechanisms contributing to the lack of a full range of effector functions observed in T cells following their stimulation by suboptimal ligands. Finally, we present strategies for the design of peptide-based therapies to control activation of polyclonal, autoreactive T-cell populations.