{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lever M"],"funding":["Medical Research Council","Royal Society","Wellcome Trust","Engineering and Physical Sciences Research Council"],"pagination":["E6630-E6638"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5087047"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["113(43)"],"pubmed_abstract":["T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose-response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model corr"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose."],"pmcid":["PMC5087047"],"funding_grant_id":["1512113","MR/J002011/1","G9722488","098363","101799/Z/13/Z","G19/31","101799","100262/Z/12/Z"],"pubmed_authors":["Lim HS","Dushek O","Lever M","Kruger P","Trendel N","van der Merwe PA","Abu-Shah E","Maini PK","Nguyen J"],"additional_accession":[]},"is_claimable":false,"name":"Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose.","description":"T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose-response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model corr","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Oct","modification":"2025-04-22T08:56:49.34Z","creation":"2019-03-27T02:27:52Z"},"accession":"S-EPMC5087047","cross_references":{"pubmed":["27702900"],"doi":["10.1073/pnas.1608820113"]}}