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Dimensions and Interactions of Large T-Cell Surface Proteins

Junghans, Victoria LU ; Santos, Ana Mafalda; Lui, Yuan; Davis, Simon J. and Jönsson, Peter LU (2018) In Frontiers in Immunology 9.
Abstract

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,... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CD45, glycoproteins, hydrodynamic trapping, kinetic-segregation model, protein dimensions, protein interactions
in
Frontiers in Immunology
volume
9
pages
1 pages
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85054898765
ISSN
1664-3224
DOI
10.3389/fimmu.2018.02215
language
English
LU publication?
yes
id
ee1a8d48-c463-4b59-8cc2-8b63876040ea
date added to LUP
2018-11-09 12:47:31
date last changed
2019-09-04 04:28:52
@article{ee1a8d48-c463-4b59-8cc2-8b63876040ea,
  abstract     = {<p>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.</p>},
  articleno    = {02215},
  author       = {Junghans, Victoria and Santos, Ana Mafalda and Lui, Yuan and Davis, Simon J. and Jönsson, Peter},
  issn         = {1664-3224},
  keyword      = {CD45,glycoproteins,hydrodynamic trapping,kinetic-segregation model,protein dimensions,protein interactions},
  language     = {eng},
  pages        = {1},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Immunology},
  title        = {Dimensions and Interactions of Large T-Cell Surface Proteins},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.02215},
  volume       = {9},
  year         = {2018},
}