Abstract

The adaptive immune system protects the body from an ever-changing landscape of foreign pathogens. The two arms of the adaptive immune system, T cells and B cells, mount specific responses to pathogens by utilizing the diversity of their receptors, generated through hypermutation. T cells recognize and clear infected hosts when their highly variable receptors bind sufficiently strongly to antigen-derived peptides displayed on a cell surface. To avoid auto-immune responses, randomly generated receptors that bind strongly to self-peptides are eliminated in the “central” process of thymic selection, ensuring a mostly self-tolerant repertoire of mature T cells. “Peripheral” tolerance, including a quorum mechanism further protects against self-targeting T cells that escape thymic selection. We discuss how these mechanisms can still fail during persistent infections.