TCR and TLR5 merged Boolean model
Taxon: Mammal
Process: T-cell activation
Submitter: Pedro Monteiro
Supporting paper: Rodríguez-Jorge, Otoniel and Kempis-Calanis, Linda A. and Abou-Jaoudé, Wassim and Gutiérrez-Reyna, Darely Y. and Hernandez, Céline and Ramirez-Pliego, Oscar and Thomas-Chollier, Morgane and Spicuglia, Salvatore and Santana, Maria A. and Thieffry, Denis (2019). Cooperation between T cell receptor and Toll-like receptor 5 signaling for CD4+ T cell activation. Science Signaling. 10.1126/scisignal.aar3641
| Model file(s) | Description(s) |
|---|---|
| RodriguezJorge_Merged_TCR_TLR5_Signalling_BooleanModel_15Jul2018.zginml | Boolean model resulting from the merging of the two Boolean models for TCR and TLR5 signalling as listed above. This comprehensive Boolean model encompasses 128 nodes, including three externally controlled inputs (TLR5, TCR, and CD28 ) and six phenotypic nodes |
| RodriguezJorge_TLR5_Signalling_BooleanModel_17Jul2018.zginml | TLR5 Boolean model |
| RodriguezJorge_TCR_Signalling_BooleanModel_17Jul2018.zginml | TCR Boolean model |
Summary:
CD4+ T cells recognize antigens through their T cell receptors TCR). However,
additional signals involving co-stimulatory receptors, for example CD28, are
required for proper T cell activation. Alternative co-stimulatory receptors
have been proposed, including members of the Toll-like receptor family, such
as TLR5 and TLR2.
We report here three Boolean models for:
- the T cell receptor (TCR) signalling pathway;
- the Toll-like receptor (TLR5) signalling pathway;
- the combination of TCR and TLR5 pathway, taking into accounting cross-interactions.
These models were validated by analysing the responses of T cells to the activation of these pathways alone or in combination, in terms of CREB, c-Jun and p65 activation. The resulting merged model accurately reproduces the experimental results, showing that the activation of TLR5 can play a similar role to that of CD28, regarding AP-1, CREB and NF-кB activation, thereby, providing insights regarding the cross-regulation of these pathways in CD4+ T cells.
