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The T cell receptor (TCR) [Alpha]Β heterodimer interacts with its ligands with high specificity, but surprisingly low affinity. The role of the [Zeta] component of the murine TCR in contributing to the fidelity of antigen recognition was examined. With sequence-specific phosphotyrosine antibodies, it was found that [Zeta] undergoes a series of ordered phosphorylation events upon TCR engagement. Completion of phosphorylation steps is dependent on the nature of the TCR ligand. Thus, the phosphorylation steps establish thresholds for T cell activation. This study documents the sophisticated molecular events that follow the engagement of a low-affinity receptor., The [Alpha]Β TCR is part of a large protein complex composed of the CD3 [Gamma] Δ, [Epsilon], and [Zeta] chains. These chains contain signaling motifs called ITAMs (immune receptor tyrosinebased [...]

Examines the role of the ...component of the murine t cell receptor (TCR) in contributing to the fidelity of antigen recognition. How the TCR alpha-beta heterodimer interacts with ligands with high specifity but low affinity; Documentation of the molecular events that follow the engagement of the low-affinity receptor.

The article reports on the impact of blockade in calcium channel on chronic kidney disease (CKD). Topics discussed include several cause of chronic kidney disease such as obesity, hypertension and diabetes, increase in the risk of end-stage renal disease (ESRD) and role of transient receptor potential canonical-5 (TRPC5).

The immunological synapse is a specialized cell-cell junction between T cell and antigen-presenting cell surfaces. It is characterized by a central cluster of antigen receptors, a ring of integrin family adhesion molecules, and temporal stability over hours. The role of this specific organization in signaling for T cell activation has been controversial. We use in vitro and in silico experiments to determine that the immunological synapse acts as a type of adaptive controller that both boosts T cell receptor triggering and attenuates strong signals. [ABSTRACT FROM AUTHOR]

The area of contact between a T cell and an antigen-presenting cell (APC) is known as the immunological synapse. Although its exact function is unknown, one model suggests that it allows for T cell receptor (TCR) clustering and for sustained signaling in T cells for many hours. Here we demonstrate that TCR-mediated tyrosine kinase signaling in naïve T cells occurred primarily at the periphery of the synapse and was largely abated before mature immunological synapses had formed. These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation. [ABSTRACT FROM AUTHOR]