T cell receptor recognition via cooperative conformational plasticity
Autor: | Alison Wojnarowicz, Marale Damirjian, Susan J. Gagnon, William E. Biddison, Rebecca L. Davis-Harrison, Richard V. Turner, Oleg Y. Borbulevych, Brian M. Baker |
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Rok vydání: | 2006 |
Předmět: |
Protein Conformation
T cell Receptors Antigen T-Cell chemical and pharmacologic phenomena Plasma protein binding Complementarity determining region Major histocompatibility complex medicine.disease_cause Crystallography X-Ray Protein structure Cross-Priming Structural Biology HLA-A2 Antigen medicine Humans Receptor Molecular Biology biology T-cell receptor Gene Products tax Cell biology Molecular mimicry medicine.anatomical_structure Biochemistry biology.protein Protein Binding |
Zdroj: | Journal of molecular biology. 363(1) |
ISSN: | 0022-2836 |
Popis: | Although T cell receptor cross-reactivity is a fundamental property of the immune system and is implicated in numerous autoimmune pathologies, the molecular mechanisms by which T cell receptors can recognize and respond to diverse ligands are incompletely understood. In the current study we examined the response of the human T cell lymphotropic virus-1 (HTLV-1) Tax-specific T cell receptor (TCR) A6 to a panel of structurally distinct haptens coupled to the Tax 11-19 peptide with a lysine substitution at position 5 (Tax5K, LLFG[K-hapten]PVYV). The A6 TCR could cross-reactively recognize one of these haptenated peptides, Tax-5K-4-(3-Indolyl)-butyric acid (IBA), presented by HLA-A*0201. The crystal structures of Tax5K-IBA/HLA-A2 free and in complex with A6 reveal that binding is mediated by a mechanism of cooperative conformational plasticity involving conformational changes on both sides of the protein-protein interface, including the TCR complementarity determining region (CDR) loops, Valpha/Vbeta domain orientation, and the hapten-modified peptide. Our findings illustrate the complex role that protein dynamics can play in TCR cross-reactivity and highlight that T cell receptor recognition of ligand can be achieved through diverse and complex molecular mechanisms that can occur simultaneously in the interface, not limited to molecular mimicry and CDR loop shifts. |
Databáze: | OpenAIRE |
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