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Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters

The T cell receptor (TCR) interacts with peptide-major histocompatibility complex (pMHC) to enable T cell development and trigger adaptive immune responses. For this reason, TCR:pMHC interactions have been intensely studied for over two decades. However, the details of how various binding parameters...

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Autores principales: Edwards, Lindsay J., Zarnitsyna, Veronika I., Hood, Jennifer D., Evavold, Brian D., Zhu, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342060/
https://www.ncbi.nlm.nih.gov/pubmed/22566966
http://dx.doi.org/10.3389/fimmu.2012.00086
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author Edwards, Lindsay J.
Zarnitsyna, Veronika I.
Hood, Jennifer D.
Evavold, Brian D.
Zhu, Cheng
author_facet Edwards, Lindsay J.
Zarnitsyna, Veronika I.
Hood, Jennifer D.
Evavold, Brian D.
Zhu, Cheng
author_sort Edwards, Lindsay J.
collection PubMed
description The T cell receptor (TCR) interacts with peptide-major histocompatibility complex (pMHC) to enable T cell development and trigger adaptive immune responses. For this reason, TCR:pMHC interactions have been intensely studied for over two decades. However, the details of how various binding parameters impact T cell activation remain elusive. Most measurements were made using recombinant proteins by surface plasmon resonance, a three-dimensional (3D) technique in which fluid-phase receptors and ligands are removed from their cellular environment. This approach found TCR:pMHC interactions with relatively low affinities and slow off-rates for agonist peptides. Newer generation techniques have analyzed TCR:pMHC interactions in two dimensions (2D), with both proteins anchored in apposing plasma membranes. These approaches reveal in situ TCR:pMHC interaction kinetics that are of high affinity and exhibit rapid on- and off-rates upon interaction with agonist ligands. Importantly, 2D binding parameters correlate better with T cell functional responses to a spectrum of ligands than 3D measures.
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spelling pubmed-33420602012-05-07 Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters Edwards, Lindsay J. Zarnitsyna, Veronika I. Hood, Jennifer D. Evavold, Brian D. Zhu, Cheng Front Immunol Immunology The T cell receptor (TCR) interacts with peptide-major histocompatibility complex (pMHC) to enable T cell development and trigger adaptive immune responses. For this reason, TCR:pMHC interactions have been intensely studied for over two decades. However, the details of how various binding parameters impact T cell activation remain elusive. Most measurements were made using recombinant proteins by surface plasmon resonance, a three-dimensional (3D) technique in which fluid-phase receptors and ligands are removed from their cellular environment. This approach found TCR:pMHC interactions with relatively low affinities and slow off-rates for agonist peptides. Newer generation techniques have analyzed TCR:pMHC interactions in two dimensions (2D), with both proteins anchored in apposing plasma membranes. These approaches reveal in situ TCR:pMHC interaction kinetics that are of high affinity and exhibit rapid on- and off-rates upon interaction with agonist ligands. Importantly, 2D binding parameters correlate better with T cell functional responses to a spectrum of ligands than 3D measures. Frontiers Research Foundation 2012-04-20 /pmc/articles/PMC3342060/ /pubmed/22566966 http://dx.doi.org/10.3389/fimmu.2012.00086 Text en Copyright © 2012 Edwards, Zarnitsyna, Hood, Evavold and Zhu. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Immunology
Edwards, Lindsay J.
Zarnitsyna, Veronika I.
Hood, Jennifer D.
Evavold, Brian D.
Zhu, Cheng
Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters
title Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters
title_full Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters
title_fullStr Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters
title_full_unstemmed Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters
title_short Insights into T Cell Recognition of Antigen: Significance of Two-Dimensional Kinetic Parameters
title_sort insights into t cell recognition of antigen: significance of two-dimensional kinetic parameters
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342060/
https://www.ncbi.nlm.nih.gov/pubmed/22566966
http://dx.doi.org/10.3389/fimmu.2012.00086
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