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Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions

The crystal structures of the 2C/H-2K(bm3)–dEV8 allogeneic complex at 2.4 Å and H-2K(bm3)–dEV8 at 2.15 Å, when compared with their syngeneic counterparts, elucidate structural changes that induce an alloresponse. The Asp77Ser mutation that imbues H-2K(bm3)–dEV8 with its alloreactive properties is lo...

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Autores principales: Luz, John G., Huang, Mingdong, Garcia, K. Christopher, Rudolph, Markus G., Apostolopoulos, Vasso, Teyton, Luc, Wilson, Ian A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193710/
https://www.ncbi.nlm.nih.gov/pubmed/11994422
http://dx.doi.org/10.1084/jem.20011644
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author Luz, John G.
Huang, Mingdong
Garcia, K. Christopher
Rudolph, Markus G.
Apostolopoulos, Vasso
Teyton, Luc
Wilson, Ian A.
author_facet Luz, John G.
Huang, Mingdong
Garcia, K. Christopher
Rudolph, Markus G.
Apostolopoulos, Vasso
Teyton, Luc
Wilson, Ian A.
author_sort Luz, John G.
collection PubMed
description The crystal structures of the 2C/H-2K(bm3)–dEV8 allogeneic complex at 2.4 Å and H-2K(bm3)–dEV8 at 2.15 Å, when compared with their syngeneic counterparts, elucidate structural changes that induce an alloresponse. The Asp77Ser mutation that imbues H-2K(bm3)–dEV8 with its alloreactive properties is located beneath the peptide and does not directly contact the T cell receptor (TCR). However, the buried mutation induces local rearrangement of the peptide itself to preserve hydrogen bonding interactions between the peptide and the α(1) 77 residue. The COOH terminus of the peptide main chain is tugged toward the α(1)-helix such that its presentation to the TCR is altered. These changes increase the stability of the allogeneic peptide-major histocompatibility complex (pMHC) complex and increase complementarity in the TCR–pMHC interface, placing greater emphasis on recognition of the pMHC by the TCR β-chain, evinced by an increase in shape complementarity, buried surface area, and number of TCR–pMHC contacting residues. A nearly fourfold increase in the number of β-chain–pMHC contacts is accompanied by a concomitant 64% increase in β-chain–pMHC shape complementarity. Thus, the allogeneic mutation causes the same peptide to be presented differently, temporally and spatially, by the allogeneic and syngeneic MHCs.
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spelling pubmed-21937102008-04-14 Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions Luz, John G. Huang, Mingdong Garcia, K. Christopher Rudolph, Markus G. Apostolopoulos, Vasso Teyton, Luc Wilson, Ian A. J Exp Med Article The crystal structures of the 2C/H-2K(bm3)–dEV8 allogeneic complex at 2.4 Å and H-2K(bm3)–dEV8 at 2.15 Å, when compared with their syngeneic counterparts, elucidate structural changes that induce an alloresponse. The Asp77Ser mutation that imbues H-2K(bm3)–dEV8 with its alloreactive properties is located beneath the peptide and does not directly contact the T cell receptor (TCR). However, the buried mutation induces local rearrangement of the peptide itself to preserve hydrogen bonding interactions between the peptide and the α(1) 77 residue. The COOH terminus of the peptide main chain is tugged toward the α(1)-helix such that its presentation to the TCR is altered. These changes increase the stability of the allogeneic peptide-major histocompatibility complex (pMHC) complex and increase complementarity in the TCR–pMHC interface, placing greater emphasis on recognition of the pMHC by the TCR β-chain, evinced by an increase in shape complementarity, buried surface area, and number of TCR–pMHC contacting residues. A nearly fourfold increase in the number of β-chain–pMHC contacts is accompanied by a concomitant 64% increase in β-chain–pMHC shape complementarity. Thus, the allogeneic mutation causes the same peptide to be presented differently, temporally and spatially, by the allogeneic and syngeneic MHCs. The Rockefeller University Press 2002-05-06 /pmc/articles/PMC2193710/ /pubmed/11994422 http://dx.doi.org/10.1084/jem.20011644 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Luz, John G.
Huang, Mingdong
Garcia, K. Christopher
Rudolph, Markus G.
Apostolopoulos, Vasso
Teyton, Luc
Wilson, Ian A.
Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions
title Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions
title_full Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions
title_fullStr Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions
title_full_unstemmed Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions
title_short Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V(β) Interactions
title_sort structural comparison of allogeneic and syngeneic t cell receptor–peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing v(β) interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193710/
https://www.ncbi.nlm.nih.gov/pubmed/11994422
http://dx.doi.org/10.1084/jem.20011644
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