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| '''Human Class I MHC HLA-A2 in complex with the modified HTLV-1 TAX (Y5K-4-[3-Indolyl]-butyric acid) peptide'''
| | ===Human Class I MHC HLA-A2 in complex with the modified HTLV-1 TAX (Y5K-4-[3-Indolyl]-butyric acid) peptide=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16962135}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16962135 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16962135}} |
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| ==Disease== | | ==Disease== |
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| [[Category: Mhc class i,hla-a2]] | | [[Category: Mhc class i,hla-a2]] |
| [[Category: X-ray crystallography]] | | [[Category: X-ray crystallography]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:09:17 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:22:16 2008'' |
