T cell receptor recognition via cooperative conformational plasticity.

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T cell receptor recognition via cooperative conformational plasticity. Abstract Text:

Susan J Gagnon,Oleg Y Borbulevych,Rebecca L Davis-Harrison,Richard V Turner,Marale Damirjian,Alison Wojnarowicz,William E Biddison,Brian M Baker,

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.

T cell receptor recognition via cooperative conformational plasticity. Publishing Authors By Initials

SJ Gagnon,OY Borbulevych,RL Davis-Harrison,RV Turner,M Damirjian,A Wojnarowicz,WE Biddison,BM Baker,

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T cell receptor recognition via cooperative conformational plasticity. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of molecular biology

VOLUME: 363

Page Numbers: 228-43

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ISSN: 0022-2836

DAY: 22

MONTH: 08

YEAR: 2006

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LANGUAGE: eng

NlmUniqueID: 2985088

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AFFILIATION: Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Country: England

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MEDLINETA: J Mol Biol

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