Figure 1.
Superposition of H-2Db-H-2Kb -restricted epitopes.
Structures of five H-2Db -restricted epitopes (1CE6, 1S7V, 1WBZ, 1ZHB and 3BUY) and of five H-2Kb-restricted epitopes (1FO0, 1FZJ, 1LK2, 1RJY and 1S7R) were superposed. The color pattern was kept on figures A, B and C. A: The side view shows the conformational differences among the H-2Db (red) and the H-2Kb –restricted epitopes (blue), especially between positions 5 and 7 (p5-7). B: Top view of the 10 superposed peptides. C: Two crystal structures (1S7V and 1S7R) representing the same epitope (KAVYNLATM) in the context of these two different alleles.
Figure 2.
Conformational pattern of H-2Db-restricted epitopes.
A: Crystal structures of 28 epitopes (Table 1) - size range between 8 and 11 amino acids - were superposed. It is possible to observe the existence of a shared pattern among the epitopes main chains (backbone). The orientation (N-terminal to C-terminal) was kept. B: Top view of the same 28 epitopes. C: Only the epitopes with nine amino acids were superposed, showing that the variability among the epitopes structure is determined by differences in length. The side chains of the epitopes were not represented in these images, and an amino acid (p7) of epitope 2VE6 (altered photocleavable peptide) was excluded.
Figure 3.
Interactions between epitope and MHC cleft.
A: Images of H-2Db (1CE6) and H-2Kb (1RJY) complexes are generated with Chimera package. Position of the complexes is indicated in the Side View Window (A1,B1,C1,D1). H-2Db-restricted peptide is depicted in red (A, B) and H-2Kb-restricted peptide is depicted in blue (C,D). MHC side chains that interact with the peptide are represented as sticks and Hydrogen bonds are represented as light blue lines. The MHC Alpha-1 domain (α1) and the first position of the peptide (p1) are indicated, as also some amino acid labels.
Table 1.
List of H-2Db ligands available at PDB.
Table 2.
Reproduction of pMHC crystal structures.
Figure 4.
Topology and electrostatic potential comparison among A2*0201:HCV complexes.
TCR-interacting surfaces of ten different pMHC complexes are depicted (C–L). Regions with positive (blue) and negative (red) charges are represented with a scale from −10 to +10 kiloteslas. Sequence of presented peptide is depicted above each complex and the position of the Alanine exchange is depicted in red. Alpha-1 and Alpha-2 MHC domains are also indicated. Images A, B and C show the same pMHC, in the same position, size and orientation, although with different representations. TCR-interacting surfaces of complexes that stimulate high levels of IFN-γ production by CVNGVCWTV-specific CD8+ T-cells (J,K and L) shared both topology and electrostatic potential. One complex that stimulates low levels of IFN-γ production (G) presented differences in topology and reduction of a negatively charged region in the TCR-interacting surface.