Figure 6.

Differences in Flexibility between the aeTCRs Variable Regions and Their Counterpart WT TCRs

(A) ΔRMSF values (aeTCR variant RMSF-WT 1G4 TCR RMSF) for the 1G4-derived aeTCRs, with the top panels corresponding to the CDRα and CDRβ of the apo TCRs, and bottom panels corresponding to CDRα and CDRβ of the TCRs in complex with pHLA. (B) ΔRMSF values (aeTCR variant RMSF-WT TCR RMSF) for the MEL5-, DMF5-, and A6-derived aeTCRs, with top panels corresponding to the CDRα and CDRβ of the apo TCRs, and bottom panels corresponding to CDRα and CDRβ of the TCRs in complex with pHLA. A more negative ΔRMSF value indicates increased rigidity for the aeTCR variant relative to the WT TCR. The points toward the bottom of each graph indicate residues with significantly different ΔRMSF values as determined by a two-sample t test (p < 0.05). The numbers boxed in red represent regions of each aeTCR that increase rigidity compared to the WT TCRs in the pHLA bound form. Complete RMSF plots for all TCRs simulated are provided in Figures S4–S7. (C) For each region of the aeTCRs where increased rigidity compared to the WT TCRs in pHLA bound form was observed (marked by numbers in red boxes), the corresponding CDR or HV4 loop of the TCR is shown (as cartoon colored in accordance with A and B) with mutations from WT TCR to aeTCR labeled (shown as red sticks). Black arrows show which regions of the TCR-pHLA complex are near each loop, to provide a potential mechanism for the increases in rigidity detected.