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Related Experiment Videos

CD4 and CD8 molecules can physically associate with the same T-cell receptor.

P F Gallagher1, B Fazekas de St Groth, J F Miller

  • 1Thymus Biology Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

Proceedings of the National Academy of Sciences of the United States of America
|December 1, 1989
PubMed
Summary

Cell surface glycoproteins CD4 and CD8 associate with the T-cell receptor (TCR) to enhance T cell adhesion to antigen-presenting cells. This interaction is crucial for optimal T-cell receptor triggering during antigen recognition.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD4 and CD8 glycoproteins on T cells typically correlate with MHC class II and class I restriction, respectively.
  • These molecules bind MHC molecules on antigen-presenting cells (APCs), enhancing T cell-APC adhesion.
  • Previous studies suggested CD4 and CD8 physically interact with the T-cell receptor (TCR) during antigen recognition.

Purpose of the Study:

  • To identify proteins copurifying with CD4.
  • To investigate the association of TCR with CD4 and CD8 in T cells.
  • To determine if CD4 and CD8 distinguish between MHC class I and class II-restricted TCRs.

Main Methods:

  • Affinity chromatography and two-dimensional diagonal gel electrophoresis were used to isolate proteins associated with CD4.

Related Experiment Videos

  • Preclearing with an anti-TCR antibody (F23.1) and protease digestion were employed for protein identification.
  • Isolation of CD4 and CD8 from a CD4+ CD8+ T-cell clone was performed to study TCR association.

    • Main Results:

    • A Mr 43,000 disulfide-bonded heterodimer, identified as the TCR, was found to copurify with CD4.
    • The TCR was observed to associate with either CD4 or CD8 in a CD4+ CD8+ T-cell clone, even without activation.
    • These findings indicate that CD4 and CD8 can form membrane complexes with both class I- and class II-restricted TCRs.

    Conclusions:

    • CD4 and CD8 do not differentiate between MHC class I- and class II-restricted TCRs in their ability to form membrane complexes.
    • Optimal T-cell receptor triggering requires recognition of the same MHC molecule by both the TCR and its associated accessory molecule (CD4 or CD8).
    • This study elucidates the molecular interactions between TCR, CD4, CD8, and MHC molecules, crucial for T cell activation.