You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Costimulatory receptor mechanisms
In addition to receiving antigen-driven signals through their T cell receptors (TCRs), CD4+ T cells also require activation of the costimulatory receptor CD28 to ensure full activation. Rodríguez-Jorge et al. combined mathematical modeling of signaling by the TCR and by the pattern recognition receptor Toll-like receptor (TLR5) to predict how the two pathways could combine to induce T cell activation. Experiments then showed how the TCR and TLR5 pathways converged on the activation of critical transcriptional regulators needed for T cell activation, suggesting that TLR5 plays a role similar to that of CD28 in T cell activation.
Abstract
CD4+ T cells recognize antigens through their T cell receptors (TCRs); however, additional signals involving costimulatory receptors, for example, CD28, are required for proper T cell activation. Alternative costimulatory receptors have been proposed, including members of the Toll-like receptor (TLR) family, such as TLR5 and TLR2. To understand the molecular mechanism underlying a potential costimulatory role for TLR5, we generated detailed molecular maps and logical models for the TCR and TLR5 signaling pathways and a merged model for cross-interactions between the two pathways. Furthermore, we validated the resulting model by analyzing how T cells responded to the activation of these pathways alone or in combination, in terms of the activation of the transcriptional regulators CREB, AP-1 (c-Jun), and NF-κB (p65). Our merged model accurately predicted the experimental results, showing that the activation of TLR5 can play a similar role to that of CD28 activation with respect to AP-1, CREB, and NF-κB activation, thereby providing insights regarding the cross-regulation of these pathways in CD4+ T cells.
This is an article distributed under the terms of the Science Journals Default License.
