Functional development of the T cell receptor for antigen

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Item Type:	Review
Title:	Functional development of the T cell receptor for antigen
Creators Name:	Ebert, P.J.R., Li, Q.J., Huppa, J.B. and Davis, M.M.
Abstract:	For over three decades now, the T cell receptor (TCR) for antigen has not ceased to challenge the imaginations of cellular and molecular immunologists alike. T cell antigen recognition transcends every aspect of adaptive immunity: it shapes the T cell repertoire in the thymus and directs T cell-mediated effector functions in the periphery, where it is also central to the induction of peripheral tolerance. Yet, despite its central position, there remain many questions unresolved: how can one TCR be specific for one particular peptide-major histocompatibility complex (pMHC) ligand while also binding other pMHC ligands with an immunologically relevant affinity? And how can a T cell's extreme specificity (alterations of single methyl groups in their ligand can abrogate a response) and sensitivity (single agonist ligands on a cell surface are sufficient to trigger a measurable response) emerge from TCR-ligand interactions that are so low in affinity? Solving these questions is intimately tied to a fundamental understanding of molecular recognition dynamics within the many different contexts of various T cell-antigen presenting cell (APC) contacts: from the thymic APCs that shape the TCR repertoire and guide functional differentiation of developing T cells to the peripheral APCs that support homeostasis and provoke antigen responses in naïve, effector, memory, and regulatory T cells. Here, we discuss our recent findings relating to T cell antigen recognition and how this leads to the thymic development of foreign-antigen-responsive alphabetaT cells.
Keywords:	T Cell Receptor, MHC, Thymus, Positive Selection, MicroRNA, Immunological Synapse, Heterodimer, Peptide, Animals
Source:	Progress in Molecular Biology and Translational Science
ISSN:	1877-1173
Publisher:	Elsevier / Academic Press
Volume:	92
Page Range:	65-100
Date:	2010
Official Publication:	https://doi.org/10.1016/S1877-1173(10)92004-8
PubMed:	View item in PubMed

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