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Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

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CD8 Co-Receptor Enhances T-Cell Activation without Any Effect on Initial Attachment.

Philippe Robert1,2, Laurent Limozin1, P Anton van der Merwe3

  • 1Laboratoire Adhesion et Inflammation, UMR INSERM 1067, UMR CNRS 7333, Aix-Marseille Université, Case 937, CEDEX 09, 13288 Marseille, France.

Cells
|March 6, 2021
PubMed
Summary
This summary is machine-generated.

The T-cell receptor (TCR) and CD8 co-receptor work together to help T lymphocytes detect antigens. CD8 enhances T-cell spreading responses after initial contact, rather than directly impacting TCR-pMHC binding.

Keywords:
2D binding kineticsT-cell receptorT-cell triggeringinterference reflection microscopylaminar flow chamberreflection interference contrast microscopyspreading

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Area of Science:

  • Immunology
  • Cellular Biology
  • Biophysics

Background:

  • T lymphocytes (T cells) are crucial for adaptive immunity, identifying foreign antigens presented by peptide-major histocompatibility complexes (pMHCs).
  • T-cell receptor (TCR) engagement with pMHCs initiates T cell activation, a process influenced by co-receptors like CD8.
  • The precise role of CD8 in modulating TCR-pMHC interactions and subsequent T cell responses remains incompletely understood.

Purpose of the Study:

  • To investigate the role of CD8 in T-cell interactions with pMHCs at the single-molecule level.
  • To elucidate the kinetics of T-cell receptor (TCR) and CD8 co-receptor binding and T cell spreading responses.
  • To determine how varying pMHC activating strengths affect TCR-pMHC interactions and T cell spreading.

Main Methods:

  • Utilized a laminar flow chamber to measure single-molecule bond kinetics between TCR-transfected Jurkat cells (CD8+ and CD8-) and surfaces coated with various pMHCs.
  • Employed interference reflection microscopy to visualize and quantify T cell spreading on pMHC-presenting surfaces.
  • Analyzed the initial contact, bond formation/rupture, and spreading dynamics in response to different pMHC ligands.

Main Results:

  • CD8 did not significantly alter the initial TCR-pMHC interaction kinetics within the first few seconds of cell contact.
  • CD8 markedly promoted subsequent T cell spreading responses, indicating a role in early activation rather than initial binding.
  • The rate and extent of T cell spreading were dependent on the activating strength of the pMHC, while the lag time to spreading initiation was not.
  • TCR-pMHC bond kinetics and cell spreading dynamics provide insights into T cell detection strategies.

Conclusions:

  • CD8 acts as an enhancer of T cell activation and spreading, downstream of initial TCR-pMHC binding.
  • T cell detection of antigens involves a dynamic interplay between TCR-pMHC interactions and co-receptor signaling.
  • Understanding these mechanisms can illuminate T cell signaling networks and inform therapeutic strategies in immunology.