Selective modulation of protein kinase C-Θ during T-cell activation

Abstract

Every cell contains many families of protein kinases, and may express several structurally related yet genetically distinct kinases of each family. The activity of the serine/threonine protein kinase C (PKC) enzymes has long been implicated in T-cell activation, but it is not known which members of the PKC family regulate the T-cell response to foreign antigens. The activation of T cells by antigen-presenting cells (APCs) is spatially restricted to their site of contact, where receptors on the T cells engage their counter-receptors on the APCs. We used this localized engagement to identify, at the single-cell level, intracellular proteins involved in the activation process. By digital immunofluorescence microscopy, we localized six isoforms of PKC in antigen-specific T-cell clones activated by APCs. Surprisingly, only PKC-theta translocated to the site of cell contact. Accordingly, in vitro kinase activity assays of PKC immunoprecipitates from the conjugates of T cells and APCs showed a selective increase in the activity of PKC-theta, indicating that the translocated enzyme is active. Several modes of partial T-cell activation that failed to cause PKC-theta translocation also failed to cause T-cell proliferation, further suggesting the involvement of PKC-theta in T-cell activation.

Continued Antigen Stimulation Is Not Required During CD4+ T Cell Clonal Expansion

“…6). This time frame is similar to that needed to form an immunological synapse and complete TCR-mediated signal transduction (37)(38)(39). However, this is also a shorter time than that previously indicated by other studies in which 12-24 h of TCR clustering were required to prime cells for proliferation (4).…”

FuRMAS: triggering myoblast fusion in Drosophila

“…The immunological synapse is a transient adhesive structure that connects an antigenpresenting cell (APC) with a T-cell (Monks et al, 1997;Shaw and Dustin, 1997;Grakoui et al, 1999). In terms of transient cell adhesion and local Factin branching, this structure is similar to the FuRMAS that is formed between fcs/growing myotubes and fcms during myoblast fusion.…”

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…Subsequent (within minutes) to specific interactions of T cells with APCs, TCR and MHC molecules are assembled at the centre of supramolecular activation clusters at the site of T cell contact (2,(45)(46)(47). TCR-down-regulation is observed following interactions of TCR with pMHC complexes (48)(49)(50) and T cell-APC interactions cause APC-derived surface molecules to adhere to the surface of T cells (51,52).…”