Figures and data
Simulation systems constructed based on PDB 1BD2 (Ding et al., 1998).
Extensions of B7low and B7high were selected to yield average low and high loads among simulations scanning different extensions (see Methods). Average load is calculated after 500 ns. The standard deviation (std) in load as measured in 40-ns intervals after 500 ns is shown in parentheses.
B7 TCR-pMHC interface. (A) Overview of the base complex used in simulations. Load was applied by holding the Cα atoms of terminal residues (blue spheres at the ends of “added strands”) at a given distance from each other. β2m: β2 microglobulin. (B) Magnified view of red box in panel A showing labeled CDR loops and side chains of peptide residues in stick representation. (C) Number of contacts with greater than 50% average occupancy and 80% maximum instantaneous occupancy after the initial 500 ns. Bars: std. Criteria for counting contacts and values for A6 are from Chang-Gonzalez et al. (2024). (D) Total contact occupancy measured in 40-ns overlapping intervals starting from 200 ns. TCR-pMHC (top; intermolecular) and intra-TCR (bottom; intramolecular) contacts are shown separately. Intra-TCR contacts exclude Cα-Cβ contacts (Methods). Circles with outline: B7high; without outline: B7low. Horizontal bar below each panel: B70.
Load dependent behavior of the B7 TCR-pMHC interface. (A–D) Contact occupancy heat maps. (A) B70, (B) B7low, (C) B7high, and (D) Vαβ-pMHC. Contacts with overall occupancy greater than 30% and instantaneous occupancy greater than 80% are shown. hb: hydrogen bond, np: nonpolar contact. Gray arrow in panel D denotes the approximate time when the initial adjustment of contacts in Vαβ-pMHC ends (Figure 3B). (E) Location of V-module residues forming contacts with pMHC with greater than 50% average occupancy. The last frame of each simulation is used for visualization. The backbone of the Tax peptide is shown as a purple tube. CDRs are labeled in the first panel. (F) RMSF of peptide backbone Cα atoms after 500 ns. Cα atoms were aligned to those at the beginning of the production run for RMSF calculation.
Additional characterization of the TCR-pMHC interface. (A) Number of MHC-Vα, MHC-Vβ, peptide-Vα, and peptide-Vβ contacts in A6 and B7 TCRs. Data for A6 are from Chang-Gonzalez et al. (2024). (B) Hamming distance ℋ. Histograms were calculated using data after the first 500 ns. (C) Total (pink) and per-residue (blue) BSA for interfacial residues after the first 500 ns. (D) Top row: pMHC residues forming contacts with the V-module with average occupancy greater than 50% in the high-load case. MHC residues are shown as sticks and Cα atoms of the peptide residues are shown as spheres. Viewing direction is the same as in Figure 2E. Bottom row: V-module residues forming contacts with pMHC residues in top row, shown as spheres. Residues for B7high correspond to those in Figure 2E. (E) Distance between the V-module and pMHC. Histograms were calculated using data after the first 500 ns. For Vαβ-pMHC and B7high, avg±std after 500 ns are 32.5±0.31 Å and 31.9±0.30 Å, respectively. Dashed line is the value from the crystal structure (31.6 Å).
B7 TCR chassis motion. (A) Number of Vα-Vβ contacts with greater than 50% average occupancy and 80% maximum instantaneous occupancy after the initial 500 ns. Bars: std. (B) V-module triads {e1, e2, e3}. Arrows denote directions of the first 3 PC modes for B7high as an example. CDR3s are labeled. (C) Amplitudes for the first 6 PCs. PCA was performed after 500 ns. Transparent bands: std for PCA performed in three overlapping intervals (500–800 ns, 600–900 ns, and 700–1000 ns). (D) Histograms of the V-module triad angles. (E) CDR3 distance vs. triad angles. Transparent bands: std. (F) Number of V-C contacts for each chain measured with the same criteria as in panel A. (G) Average BOC for B7low and B7high. The V-module of B7highis less bent compared to B7low. The arrows for the first 3 V-C PC modes are shown, where PC1 corresponds to the V-C bending motion. (H) Dot products computed between the BOC PC vectors of listed systems. Values closer to 1.0 denote similar V-C BOC direction of motion. (I) V-C PC amplitudes for the first 6 PC modes. Transparent bands: std measured in the same way as in panel C. (J) Differences in amplitudes for the first 3 PCs between matching V– and H-elements of α and β chains. (K) Histograms of hinge angles defined in panel G. (L) CDR3 distance versus hinge angles. Transparent bands: std. (M) V-C hinge angle trajectories over time.
