Many models have been proposed to explain the molecular mechanism underlying TCR discrimination. The TCR conformational change model postulates that a conformational change in a TCR occurs upon pMHC binding, but no conformational changes at the TCR–pMHC binding interface have been identified that are ...
DNA-barcoded pMHC multimers provide a powerful way to simultaneously label T cells recognizing distinct epitopes. This approach was recently used by 10x Genomics to identify and sequence T cells specific for 44 different epitopes38. In this assay, the binding specificity of a T cell was determined...
Immobile MCC:I-Ek surfaces were used to maximize the formation of putative CD4 docking sites along the TCR-CD3-pMHC axis (Figures S7A and S7B). The lower level of CD4TP281E expression compared with CD4T or CD4TP228E+F231E cells was accounted for by analyzing subsets of cells matched ...
involving the systematic replacement of each peptide residue with alanine. This identifies the combination of amino acids necessary for TCR binding to the pMHC complex [147,148]. However, alanine scanning does not account for the potential substitution...
To shed light on this in a comprehensive manner, we have developed a microscopy-based assay, which allows us to quantitate TCR-pMHC interactions in situ, i.e., within the special confines of the nascent immunological synapse of a T-cell contacting a planar-supported lipid bilayer functionalized...
The relevant question here is whether mature T cells with high innate self-pMHC reactivity, for example, naïve T cells with high expression of CD5 (CD5hi cells), show lower TCR sensitivity than CD5lo cells. In fact, there is evidence against this idea. Thus, for naïve T cells, ...
Comparing to a generic two-state model, our models can distinguish class I from class II MHCs and correlate their structural parameters with the TCR/pMHC’s potency to trigger T cell activation. The models are tested by mutagenesis using an MHC and a TCR mutated to alter conformation changes....
Engagement of the T cell receptor (TCR) by stimulatory ligand results in the rapid formation of microclusters at sites of T cell activation. Whereas microclusters have been studied extensively using confocal microscopy, the spatial and kinetic relationsh
, which target proteosomally processed epitopes derived from intracellular, surface bound, and secreted antigens [18]. ImmTACs are comprised of soluble, high-affinity (pico-Molar) monoclonal TCRs (mTCRs) specific for antigen-derived pMHC complexes, combined with a humanized anti-CD3 scFv domain...
1. In this study, the sourcing of biological samples from different patients with cancer will help to identify common immune markers of CD103+T cells that can modulate protective antitumor immunity beyond the interaction between the TCR and a peptide in the major histocompatibility complex (pMHC)....