Dimensions and interactions of large T-cell surface proteins

The first step of the adaptive immune response involves the interaction of T cells that express T-cell receptors (TCRs) with peptide-loaded major histocompatibility complexes expressed by antigen-presenting cells (APCs). Exactly how this leads to activation of the TCR and to downstream signaling is...

Volledige beschrijving

Bibliografische gegevens
Hoofdauteurs: Junghans, V, Santos, AM, Lui, Y, Davis, SJ, Jönsson, P
Formaat: Journal article
Taal:English
Gepubliceerd in: Frontiers Media 2018
_version_ 1826304156760014848
author Junghans, V
Santos, AM
Lui, Y
Davis, SJ
Jönsson, P
author_facet Junghans, V
Santos, AM
Lui, Y
Davis, SJ
Jönsson, P
author_sort Junghans, V
collection OXFORD
description The first step of the adaptive immune response involves the interaction of T cells that express T-cell receptors (TCRs) with peptide-loaded major histocompatibility complexes expressed by antigen-presenting cells (APCs). Exactly how this leads to activation of the TCR and to downstream signaling is uncertain, however. Recent findings suggest that one of the key events is the exclusion of the large receptor-type tyrosine phosphatase CD45, from close contacts formed at sites of T-cell/APC interaction. If this is true, a full understanding of how close contact formation leads to signaling would require insights into the structures of, and interactions between, large membrane proteins like CD45 and other proteins forming the glycocalyx, such as CD43. Structural insights into the overall dimensions of these proteins using crystallographic methods are hard to obtain, and their conformations on the cell surface are also unknown. Several imaging-based optical microscopy techniques have however been developed for analyzing protein dimensions and orientation on model cell surfaces with nanometer precision. Here we review some of these methods with a focus on the use of hydrodynamic trapping, which relies on liquid flow from a micropipette to move and trap membrane-associated fluorescently labeled molecules. Important insights that have been obtained include (i) how protein flexibility and coverage might affect the effective heights of these molecules, (ii) the height of proteins on the membrane as a key parameter determining how they will distribute in cell-cell contacts, and (iii) how repulsive interactions between the extracellular parts of the proteins influences protein aggregation and distribution.
first_indexed 2024-03-07T06:13:31Z
format Journal article
id oxford-uuid:f0569c9a-25fe-459f-8f82-a3476765565a
institution University of Oxford
language English
last_indexed 2024-03-07T06:13:31Z
publishDate 2018
publisher Frontiers Media
record_format dspace
spelling oxford-uuid:f0569c9a-25fe-459f-8f82-a3476765565a2022-03-27T11:47:07ZDimensions and interactions of large T-cell surface proteinsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f0569c9a-25fe-459f-8f82-a3476765565aEnglishSymplectic Elements at OxfordFrontiers Media2018Junghans, VSantos, AMLui, YDavis, SJJönsson, PThe first step of the adaptive immune response involves the interaction of T cells that express T-cell receptors (TCRs) with peptide-loaded major histocompatibility complexes expressed by antigen-presenting cells (APCs). Exactly how this leads to activation of the TCR and to downstream signaling is uncertain, however. Recent findings suggest that one of the key events is the exclusion of the large receptor-type tyrosine phosphatase CD45, from close contacts formed at sites of T-cell/APC interaction. If this is true, a full understanding of how close contact formation leads to signaling would require insights into the structures of, and interactions between, large membrane proteins like CD45 and other proteins forming the glycocalyx, such as CD43. Structural insights into the overall dimensions of these proteins using crystallographic methods are hard to obtain, and their conformations on the cell surface are also unknown. Several imaging-based optical microscopy techniques have however been developed for analyzing protein dimensions and orientation on model cell surfaces with nanometer precision. Here we review some of these methods with a focus on the use of hydrodynamic trapping, which relies on liquid flow from a micropipette to move and trap membrane-associated fluorescently labeled molecules. Important insights that have been obtained include (i) how protein flexibility and coverage might affect the effective heights of these molecules, (ii) the height of proteins on the membrane as a key parameter determining how they will distribute in cell-cell contacts, and (iii) how repulsive interactions between the extracellular parts of the proteins influences protein aggregation and distribution.
spellingShingle Junghans, V
Santos, AM
Lui, Y
Davis, SJ
Jönsson, P
Dimensions and interactions of large T-cell surface proteins
title Dimensions and interactions of large T-cell surface proteins
title_full Dimensions and interactions of large T-cell surface proteins
title_fullStr Dimensions and interactions of large T-cell surface proteins
title_full_unstemmed Dimensions and interactions of large T-cell surface proteins
title_short Dimensions and interactions of large T-cell surface proteins
title_sort dimensions and interactions of large t cell surface proteins
work_keys_str_mv AT junghansv dimensionsandinteractionsoflargetcellsurfaceproteins
AT santosam dimensionsandinteractionsoflargetcellsurfaceproteins
AT luiy dimensionsandinteractionsoflargetcellsurfaceproteins
AT davissj dimensionsandinteractionsoflargetcellsurfaceproteins
AT jonssonp dimensionsandinteractionsoflargetcellsurfaceproteins