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| Article Authors: | A C Tissot; C Ciatto; P R Mittl; M G Grütter; A Plückthun |
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| Article 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. |
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| Reference ID: | 1000986 |
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| 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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| Affiliations: | Biochemisches Institut der Universität Zürich, Winterthurerstrasse 190, Zürich, CH-8057, Switzerland. |
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| Date: | 2000 |
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| Reference Type: | Literature |
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| PubMed ID: | 10993729 |
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| Journal: | J Mol Biol |
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| Journal Volume: | 302 |
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| Article Pages: | 873-85 |
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| Journal ISSN: | 0022-2836 |
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| Article Chemical List: | Antigens, Viral;Epitopes, T-Lymphocyte;Glycoproteins;H-2 Antigens;Ligands;Peptide Fragments;Receptors, Antigen, T-Cell;Solvents;Viral Proteins;glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus;histocompatibility antigen H-2D(b) |
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| Article MeSH List: | Amino Acid Sequence; Animals; Antigens, Viral(chemistry; genetics; immunology; isolation & purification ); Crystallography, X-Ray; Epitopes, T-Lymphocyte(chemistry; genetics; immunology; isolation & purification ); Glycoproteins(chemistry; genetics; immunology; isolation & purification ); H-2 Antigens(chemistry; immunology; isolation & purification ); Immune Tolerance(immunology ); Ligands; Lymphocytic choriomeningitis virus(genetics; immunology; physiology ); Mice; Mice, Transgenic; Models, Molecular; Molecular Sequence Data; Mutation(genetics ); Peptide Fragments(chemistry; genetics; immunology; isolation & purification ); Protein Structure, Secondary; Receptors, Antigen, T-Cell(antagonists & inhibitors; chemistry; immunology; isolation & purification ); Solvents; Surface Plasmon Resonance; Thermodynamics; Viral Proteins |
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| Curation Last Updated: | 2011-10-24 20:51:38 |
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