Figure 5.

Changes in Energetics at the TCR-pHLA Interface upon Affinity Enhancement of the A6, DMF5, and MEL5 TCRs

(A) Per-residue ΔG differences as obtained from MMGBSA analysis between the A6, DMF5, and MEL5 derived aeTCR variants and their counterpart WT TCRs (i.e., ΔΔG), with positions mutated indicated throughout in red. ΔΔG differences between the WT TCR and aeTCR pair are colored blue when ≤0.5 kcal mol^–1 (favorable for aeTCRs) and red when 0.5 kcal mol^–1 (unfavorable for aeTCRs), with all values in-between colored green. (B–G) Color mapping of the above per residue ΔΔG values onto all carbon atoms of the aeTCRs (with the WT TCR structure shown in green for reference). Color mapping is performed from blue to white to red, with blue indicating a favorable change and red indicating an unfavorable change for the aeTCRs, respectively. Figures are divided up to show the regions which show the major changes upon affinity maturation. (B) A6_c134, CDR3β; (C) DMF5_YW, CDR1α; (D) DMF5_YW, CDR3β; (E) MEL5_α24β17, CDR2β; (F) MEL5_α24β17, CDR2β; and (G) MEL5_α24β17, CDR1α and CDR3α.