Fig. 2: Ectodomains of TCR and CD4 bind cooperatively to pMHC.
From: Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity
a Pa vs tc data (points, presented as Mean ± SEM) and their model fits (curves) of pMHC-coated RBCs (38 μm−2) binding to RBCs coated with TCR alone, or a mixture of TCR and CD4 at densities (# of molecules/μm2) indicated by the numbers in legend. b Normalized whole bond number <n>w/mTCRmpMHC vs tc data (points, presented as Mean ± SEM) and their respective model fits (curves) for interactions in a. Arrow indicates decreasing density of TCR and increasing density of CD4. c Normalized trimolecular bond number <n>tri/mTCRmpMHCmCD4 vs tc data (points, presented as Mean ± SEM) and their respective model fits (curves) calculated from b by subtracting the black data from colored data followed by further normalization by mCD4. d Survival probabilities plotted as ln(# of events with lifetime greater than t) vs. bond lifetime for pMHC-coated beads interacting with beads coated with TCR, CD4, or a 1:1 mixture of TCR and CD4 measured by BFP thermal fluctuation at zero force. Each data set (points) was fitted by a straight line with the negative slope representing off-rate for TCR (k-1,TCR, n = 71) or CD4 (k-1, CD4, n = 92), or apparent off-rate for the mixed TCR and CD4 (n = 97). As a negative control, class-I MHC 9 V:HLA-A2 was used instead of TPI:HLA-DR1 to measure non-specific binding (n = 42). e Mean ± SEM bond lifetime vs force data (points), measured by BFP force-clamp experiment using beads bearing TPI:HLA-DR1 interacting with E8 TCR (n = 230), CD4 (n = 355), or a 1:1 mixture of E8 TCR and CD4 (n = 424) coated on beads, are compared with theoretical curves (mean ± SE) predicted using the model and best-fit parameters in Supplementary Fig. 3. f Model predicted trimolecular bond lifetime vs force plots for strong (red) and weak (blue) states as well as their sum (black). Data in a–c were from two independent experiments for each curve. Their model fits (mean ± SE) were calculated using Eqs. 1 and 2 based on the best-fit parameters listed in Table 1. Source data are provided as a Source Data file.
