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  • Title: Viral escape at the molecular level explained by quantitative T-cell receptor/peptide/MHC interactions and the crystal structure of a peptide/MHC complex.
    Author: Tissot AC, Ciatto C, Mittl PR, Grütter MG, Plückthun A.
    Journal: J Mol Biol; 2000 Sep 29; 302(4):873-85. PubMed ID: 10993729.
    Abstract:
    Viral escape, first characterized for the lymphocytic choriomeningitis virus (LCMV) in a mouse transgenic for the P14 T cell-receptor (TCR), can be due to mutations in T-cell epitopes. We have measured the affinity between the H-2D(b) containing the wild-type and two of its "viral escape" epitopes, as well as other altered peptide ligands (APL), by using BIACORE analysis, and solved the crystal structure of H-2D(b) in complex with the wild-type peptide at 2.75 A resolution. We show that viral escape is due to a 50 to 100-fold reduction in the level of affinity between the P14 TCR and the binary complexes of the MHC molecule with the different peptides. Structurally, one of the mutations alters a TCR contact residue, while the effect of the other on the binding of the TCR must be indirect through structural rearrangements. The former is a null ligand, while the latter still leads to some central tolerance. This work defines the structural and energetic threshold for viral escape.
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