Antigen presentation for central tolerance induction

The extent of central T cell tolerance is determined by the diversity of self-antigens that developing thymocytes ‘see’ on thymic antigen-presenting cells (APCs). Here, focusing on insights from the past decade, we review the functional adaptations of medullary thymic epithelial cells, thymic dendritic cells and thymic B cells for the purpose of tolerance induction. Their distinct cellular characteristics range from unconventional phenomena, such as promiscuous gene expression or mimicry of peripheral cell types, to strategic positioning in distinct microenvironments and divergent propensities to preferentially access endogenous or exogenous antigen pools. We also discuss how ‘tonic’ inflammatory signals in the thymic microenvironment may extend the intrathymically visible ‘self’ to include autoantigens that are otherwise associated with highly immunogenic peripheral environments. For effective central T cell tolerance, developing thymocytes must encounter a diverse range of self-antigens presented by various thymic cells. Here, the authors describe how medullary thymic epithelial cells, dendritic cells and B cells are uniquely adapted through promiscuous gene expression, strategic positioning and inflammatory signals, which shape the peptide–MHC ligandomes and extend self-antigen visibility in the thymic microenvironment.