Figure 4. HLA-CDR3 Peptide Binding.

(A and B) HLA molecule loaded with (A) CDR3 (x-Id) peptide (CARQEDTAMVYYFDYW) and (B) superagonist (SHLVEELYLVAGEEG) from Wang et al., 2018. HLA-α is shown in cyan cartoon, HLA-β is shown in silver cartoon, and epitope residues are colored by type: white, hydrophobic; green, polar; blue, basic; red, acidic.

(C) Change in binding affinity for mutating from polyglycine to the epitope for the CDR3 peptide and superagonist.

(D) Binding affinity decomposition into vdW and electrostatics (coulomb) for the CDR3 (x-Id) peptide and superagonist.

(E) van der Waals interaction energy between the HLA and epitope from MD simulation.

(F and G) Percentage of epitope residues buried in HLA for (F) CDR3 (x-Id) peptide (CARQEDTAMVYYFDYW) and (G) superagonist (SHLVEELYLVAGEEG) from Wang et al., 2018. The sequence in bold is the core epitope sequence discussed in the text.

(H) Average fluctuation (RMSF) for each residue in Å.

(I) Detailed structure of buried salt bridges between CDR3 peptide and HLA. Basic residues are in blue, acidic are in red, and epitope backbone are in tan.

(J) (Left) Overlay of most representative epitope conformations for the CDR3 peptide (light blue) and superagonist (red), with tyrosine residues in pockets 6 and 7 for the CDR3 peptide highlighted. (Right) Side view showing similar P1, P4, and P9 agreement but large differences elsewhere.

In (C)–(D), error bars are standard error across six replicas. In (E)–(H), error bars are standard error from dividing the last 250 ns of MD simulation into five sections.

See also Figure S6.