Fig. 6. Affinity and structure of the TCR LLL8–LLL–HLA-A2 complex.
a SPR analysis of TCR LLL8 binding to LLL–HLA-A2. TCR LLL8 at concentrations of 0.78, 1.56, 3.12, 6.25, 12.5, 25.0, and 50.0 μM injected over immobilized LLL–HLA-A2 (1200 RU). Kinetic fitting gave a KD of 20.4 μM. Fitting curve for equilibrium binding that resulted in a KD of 19.2 ± 1.2 μM. b Structure of the TCR LLL8–LLL–HLA-A2 complex. TCR α chain, green; TCR β chain, violet; HLA-A2 heavy chain, gray; β2microglobulin (β2m), yellow; and LLL peptide, cyan. c Positions of CDR loops of TCR LLL8 on LLL–HLA-A2 (top view). CDRs of LLL8 are shown as numbered green (CDR1α, CDR2α, and CDR3α) or violet (CDR1β, CDR2β, and CDR3β) loops. HLA-A2 is depicted as a gray surface. The LLL peptide is cyan. The green and violet spheres mark the positions of the conserved intrachain disulfide of the Vα and Vβ domains, respectively. The black dashed line indicates the crossing angle of TCR to pMHC. d Footprint of TCR LLL8 on LLL–HLA-A2. The areas contacted by individual CDR loops are color-coded: CDR1α, orange; CDR2α, cyan; CDR3α, green; CDR1β, yellow; CDR2β, blue; CDR3β, red. e Interactions between TCR LLL8 and the HLA-A2 α1 helix. The side chains of contacting residues are drawn in stick representation with carbon atoms in green (TCR α chain), violet (TCR β chain) or gray (HLA-A2). Hydrogen bonds are red dotted lines. f Interactions between TCR LLL8 and the HLA-A2 α2 helix. g Pie chart showing percentage distribution of TCR LLL8 contacts to HLA-A2 according to CDR. h Interactions between TCR LLL8 and the LLL peptide. The side chains of contacting residues are drawn in stick representation with carbon atoms in green (TCR α chain), violet (TCR β chain) or cyan (LLL). i Schematic representation of TCR LLL8–LLL interactions. Hydrogen bonds are red dotted lines and van der Waals contacts are black dotted lines. For clarity, not all van der Waals contacts are shown. j Pie chart showing percentage distribution of TCR LLL8 contacts to LLL peptide according to CDR.