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Figure 3 | Retrovirology

Figure 3

From: A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape

Figure 3

TL9-p24 exhibits a unique conformation when presented by HLA-B*81:01. Comparison of the presentation modes of HLA-B*07:02-TL9 (green sticks), HLA-B*81:01-TL9 (orange sticks) and HLA-B*42:01-TL9 (yellow sticks), the HLAI binding groove is shown as grey cartoon. (A) Structural alignment of HLA-B*07:02-TL9, HLA-B*81:01-TL9 and HLA-B*42:01-TL9 peptide conformations showing that HLA-B*07:02 and HLA-B*42:01 present TL9-p24 in identical conformations, whereas in HLA-B*81:01 residues 5–7 in TL9-p24 are presented in a distinct conformation (arrows pointing up indicate that the corresponding residue is solvent exposed and available for TCR contact, arrows pointing down indicate that the corresponding residue is buried in the HLA groove; black arrows designate that the residue is in the same orientation in all three structures, colored arrows indicate different residue conformations according to the colors used in each structure). The positions of the circled residues (Leu5, Asn6 and Thr7) may be important to explain differential escape when presented by different HLAIs. (B) HLA-B*07:02 and HLA-B*42:01 contain Trp at residue 147, compared to Leu in HLA-B*81:01. This difference generates a 1.7 Å shift in the HLAα1 helix. (C, D) This shift alters interactions between the HLAI binding groove and residues 7 and 8 in the peptide. (E) HLA-B*07:02 and HLA-B*42:01 contain Arg at residue 156 compared to Leu156 in HLA-B*81:01. This polymorphism alters interactions with the peptide leading to the observed divergent conformations. (F) TL9-p24 residue Gln3 adopts a slightly different conformation in HLA-B*07:02 and HLA-B*42:01 compared to HLA-B*81:01 which contributes to the different position of Asn6 in the peptide. (G) TL9-p24 residues Leu5 and Thr7 form a stabilising interaction in the HLA-B*81:01-TL9 structure that is not present in HLA-B*07:02-TL9, or HLA-B*42:01-TL9. (H) In HLA-B*07:02-TL9 and HLA-B*42:01-TL9, residue Leu5 is the most solvent exposed residue. However, in HLA-B*81:01-TL9, residue Asn6 assumes this role.

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