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A healthy individual can mount an immune response to exogenous pathogens while avoiding an autoimmune attack on normal tissues. The ability to distinguish between self and non-self is called 'immunological tolerance' and, for T lymphocytes, involves the generation of a diverse pool of functional T cells through positive selection and the removal of overtly(More)
T cell tolerance depends on the T cell receptor's affinity for peptide/major histocompatibility complex (MHC) ligand; this critical parameter determines whether a thymocyte will be included (positive selection) or excluded (negative selection) from the T cell repertoire. A quantitative analysis of ligand binding was performed using an experimental system(More)
Recent data using MHC/peptide tetramers and dimers suggests that the T cell coreceptors, CD4 and CD8, although important for T cell activation, do not play a direct role in facilitating T cell receptor (TCR) binding to multivalent MHC/peptide ligands. Instead, a current model proposes that coreceptors are recruited only after a stable TCR-MHC/peptide(More)
T cell clone 2C recognizes the alloantigen L(d) and the positive selecting major histocompatibility complex (MHC), K(b). To explore the molecular basis of T cell antigen receptor (TCR) binding to different peptide/MHC (pMHC) complexes, we performed alanine scanning mutagenesis of the 2C TCR. The TCR energy maps for QL9/L(d) and SIYR/K(b) were remarkably(More)
Following infection, naïve CD8+ T cells bearing pathogen-specific T cell receptors (TCRs) differentiate into a mixed population of short-lived effector and long-lived memory T cells to mediate an adaptive immune response. How the TCR regulates memory T cell development has remained elusive. Using a mutant TCR transgenic model, we found that point mutations(More)
Staining Ag-specific T cells with fluorescently labeled tetrameric MHC/peptide complexes has provided a powerful experimental approach to characterizing the immune response. In this report, we describe an extension of this method to directly visualize Ag-specific T cells in tissues. We successfully stained transgenic T cells with MHC tetramers in spleen(More)
The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was(More)
TCR engagement by peptide-MHC class I (pMHC) ligands induces a conformational change (Deltac) in CD3 (CD3Deltac) that contributes to T cell signaling. We found that when this interaction took place between primary T lineage cells and APCs, the CD8 coreceptor was required to generate CD3Deltac. Interestingly, neither enhancement of Ag binding strength nor(More)
Ab stimulation of the TCR rapidly enhances the functional activity of the LFA-1 integrin. Although TCR-mediated changes in LFA-1 activity are thought to promote T cell-APC interactions, the Ag specificity and sensitivity of TCR-mediated triggering of LFA-1 is not clear. We demonstrate that peptide/MHC (pMHC) tetramers rapidly enhance LFA-1-dependent(More)
The selection of functional T cells is mediated by interactions between the T cell antigen receptor and self-peptide major histocompatibility complex expressed on thymic epithelium. These interactions either lead to survival and development or death. The T cell antigen receptor is an unusual receptor able to signal multiple cell fates. The precise mechanism(More)