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Peptide Synthesis> | HLA-A*02:01 heavy chain (residues 1–278) with C-terminal BirA tag and β2 -microglobulin were expressed as inclusion bodies in Escherichia coli, refolded in vitro in the presence of the relevant NY-ESO-1156−165 peptide variants (SI Appendix, Table S1), and purified using size-exclusion chromatography. All peptides were purchased at >95% purity (GenScript). | Get A Quote |
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-forwar... More