Functional development of the T cell receptor for antigen

Journal Article

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 TCRligand 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 cellantigen 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 nave, 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 αβT cells. © 2010 Elsevier Inc. All rights reserved.

Full Text

Duke Authors

Cited Authors

  • Ebert, PJR; Li, QJ; Huppa, JB; Davis, MM

Published Date

  • 2010

Published In

Volume / Issue

  • 92 / C

Start / End Page

  • 65 - 100

PubMed ID

  • 20800817

Pubmed Central ID

  • 20800817

International Standard Serial Number (ISSN)

  • 1877-1173

Digital Object Identifier (DOI)

  • 10.1016/S1877-1173(10)92004-8