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CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
Journal article

CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.

  • Liu Y Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Cuendet MA Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, USA.
  • Goffin L Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Šachl R Department of Biophysical Chemistry, J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences, 18223 Prague, Czech Republic.
  • Cebecauer M Department of Biophysical Chemistry, J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences, 18223 Prague, Czech Republic.
  • Cariolato L Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Guillaume P Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Reichenbach P Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Irving M Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Coukos G Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland.
  • Luescher IF Ludwig Institute for Cancer Research, University of Lausanne, and Department of Oncology, University Hospital of Lausanne, 1009, Lausanne, Switzerland. Electronic address: immanuel.luescher@unil.ch.
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  • 2019-11-10
Published in:
  • Journal of molecular biology. - 2019
CD8
MHC
Structure
T cell
T-cell receptor
Amino Acid Sequence
Animals
CD8 Antigens
CD8-Positive T-Lymphocytes
Histocompatibility Antigens
Lymphocyte Activation
Mice
Mice, Knockout
Models, Biological
Models, Molecular
Multiprotein Complexes
Mutation
Peptides
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
Structure-Activity Relationship
English The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3. Here, we demonstrate that CD8 can also bind to pMHC on the T cell (in cis) and that this inhibits their activation. Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk. These modifications distort the stalk, thus favoring CD8 binding to pMHC in cis. Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/730
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