Engagement of the TCR by antigenic peptides presented by the MHC activates specific T cells to control infections. Recent theoretical considerations have suggested that mechanical forces acting on the TCR may be important for receptor triggering. In this study, we directly tested the hypothesis that physical forces acting on the TCR can initiate signaling in T cells by micromanipulation of indi...

The T-cell antigen receptor (TCR) is a complex of at least six different proteins (alpha, beta, gamma, delta, epsilon, and zeta) that is assembled in the endoplasmic reticulum (ER) and transported to the cell surface. Unlike mature T cells, most immature CD4+CD8+ thymocytes retain within the ER and degrade greater than 90% of some of the TCR components they synthesize, resulting in low surface ...

The pre-T cell receptor (TCR) associates with CD3-transducing subunits and triggers the selective expansion and maturation of T cell precursors expressing a TCR-beta chain. Recent experiments in pre-Talpha chain-deficient mice have suggested that the pre-TCR may not be required for signaling allelic exclusion at the TCR-beta locus. Using CD3-epsilon- and CD3-zeta/eta-deficient mice harboring a ...

We redirected the antigen specificity of primary human CD8 T cells by retrovirus-mediated transduction of genes encoding ab TCR specific to HIV-1 Pol protein. A large polyclonal population of TCR-transduced CD8 T cells showed substantial cytotoxic and cytokine production activities toward target cells either pulsed with the peptide or infected with HIV-1, and their functional activities were co...

T cells have diversity in TCR, epitope recognition, and cytokine production, and can be used for immune monitoring. Furthermore, clonal expansion of TCR families in disease may provide opportunities for TCR-directed therapies. We developed methodology for sequencing expressed genes of TCR alpha and beta chains from single cells and applied this to vaccine (tetanus-toxoid)-responsive CD4(+) T ce...

Recent evidence suggests that TCR down-regulation directly reflects the number of TCRs that have engaged MHC/peptide ligand complexes. Here, we examined the influence of defined peptides on thymic selection based on their ability to induce differential TCR internalization. Our results demonstrate that there is a direct correlation: peptides that induce strong TCR down-regulation are most effici...

Prolonged T-cell receptor (TCR) signaling is required for the proliferation of T lymphocytes. Ligation of the TCR activates signaling, but also causes internalization of the TCR from the cell surface. How TCR signaling is sustained for many hours despite lower surface expression is unknown. Using genetic inhibition of endocytosis, we show here that TCR internalization promotes continued TCR sig...

Mucosal associated invariant T (MAIT) cells are anti-microbial innate-like that abundant in blood and liver. MAIT express a semi-invariant T-cell receptor (TCR) recognizes pyrimidine ligand, derived from microbial riboflavin synthesis, bound to MR1. Both liver (ld)-MAIT can be robustly stimulated via TCR or by cytokines produced during bacterial viral infection. In this study, we compared the f...

TCR-/3 gene rearrangement or expression is necessary and sufficient for the progression of early ap thymocyte differentiation from the CD3-CD4-CD8triple negative (TN)3 to the CD4+CD8+ double positive stage. The onset of TCR-P rearrangement is currently thought to occur gradually. Some thymocytes were reported to be rearranged at the earliest (CD44+CD25-) TN stage, whereas other thymocytes did n...

The generation of a productive "in-frame" T cell receptor beta (TCR beta), immunoglobulin (Ig) heavy (H) or Ig light (L) chain variable region gene can result in the cessation of rearrangement of the alternate allele, a process referred to as allelic exclusion. This process ensures that most alphabeta T cells express a single TCR beta chain and most B cells express single IgH and IgL chains. As...