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. 2020 May 27;117(23):12826–12835. doi: 10.1073/pnas.1921964117

Fig. 4.

Fig. 4.

Contrasting TCR binding modes for recognition of KRAS-G12D neoepitopes. (A) Structures of TCR9d and TCR9a with HLA-C*08:02 and the KRAS-G12D-9-mer. TCR9d α-chain, turquoise; β-chain, orange; TCR9a α-chain, pink; β-chain, blue; HLA-C*08:02, gray; β2m, dark gray; KRAS-G12D-9-mer, green. (B) Placement of TCR9d and TCR9a CDR loops over HLA-C*08:02–KRAS-G12D-9-mer. (C) Structure of TCR10 with HLA-C*08:02 and the KRAS-G12D-10-mer. TCR10 α-chain, purple; β-chain, red; HLA-C*08:02, gray; β2m, dark gray; KRAS-G12D-10-mer, black. (D) Placement of TCR10 CDR loops over HLA-C*08:02–KRAS-G12D-10-mer. (E) Overlay of TCR9d and TCR10 with HLA-C*08:02. TCR9d and the HLA-C*08:02–9-mer complex was aligned with HLA-C*08:02 of the TCR10–HLA-C*08:02 complex. (F) Placement of TCR9d and TCR10 CDR loops over HLA-C*08:02–KRAS-G12D-10-mer. TCR9d α-chain, turquoise; β-chain, orange; TCR10 α-chain, purple; β-chain, red. (G) Crossing angles of TCR9d and TCR10 are shown in reference to the HLA-C α1-helix. Vectors are shown drawn between the centers of mass for each TCR Vα- and Vβ-chain, colored as above. Crossing angles were determined as where the TCR vector crosses the HLA-C α1-helix vector (black), drawn between positions 50 and 86 as described (2). (H) Percentage of TCR contacts with HLA-C*08:02 or peptide (Right) and percentage of TCR contacts derived from the alpha or beta chain (Left). Data were analyzed from the complex of TCR9d–HLA-C*08:02–KRAS-G12D-9-mer and TCR10–HLA-C*08:02–KRAS-G12D-10-mer. (I) Location of HLA-C*08:02 residues that form contacts in both the TCR9d and TCR10 complexes. HLA-C*08:02 residues are color-coded depending on whether the contact was with the alpha (blue) or beta (green) TCR chain. Other HLA-C residues, gray; KRAS-G12D-10-mer, black. (J) Location of HLA-C*08:02 residues that form unique contacts with TCR9d or TCR10. Color depicts HLA-C residues in contact with the TCR9d α-chain, turquoise; β-chain, orange; TCR10 α-chain, purple; β-chain, red. Other HLA-C residues, gray; KRAS-G12D-10-mer, black.