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Related Experiment Videos

Crystal structure of a soluble CD28-Fab complex.

Edward J Evans1, Robert M Esnouf, Raquel Manso-Sancho

  • 1Nuffield Department of Clinical Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.

Nature Immunology
|February 8, 2005
PubMed
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This study reveals the crystal structure of CD28, a key costimulatory protein, in complex with an antibody. This structural insight clarifies the CD28-CTLA-4-CD80-CD86 signaling system and evolutionary relationships.

Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Biology

Background:

  • Naive T cell activation depends on T cell receptor (TCR) and co-stimulatory signals.
  • CD28 is a crucial co-stimulatory protein, interacting with CD80 and CD86 on antigen-presenting cells.
  • Understanding CD28 structure is vital for deciphering T cell immune responses.

Purpose of the Study:

  • To determine the crystal structure of a soluble form of CD28 in complex with a mitogenic antibody Fab fragment.
  • To structurally compare CD28 with related proteins like CTLA-4, antigen receptors, and adhesion molecules.
  • To refine models of antibody-induced T cell receptor triggering.

Main Methods:

  • X-ray crystallography was used to obtain the structure of CD28 in complex with an antibody fragment.

Related Experiment Videos

  • Structural comparisons were performed between CD28, CTLA-4, and other related proteins.
  • Cryo-electron microscopy was employed to study CD28 complexes with different antibodies.

    • Main Results:

    • The crystal structure of soluble CD28 complexed with a mitogenic antibody Fab fragment was determined.
    • Structural comparisons provided insights into the evolutionary relationships of CD28 family members.
    • Distinct ligand-binding and stoichiometric properties of CD28 and CTLA-4 were elucidated.
    • Cryo-EM data constrained models of antibody-mediated T cell receptor triggering.

    Conclusions:

    • This work provides a comprehensive structural characterization of the CD28-CTLA-4-CD80-CD86 signaling axis.
    • The findings enhance our understanding of T cell activation mechanisms and immune regulation.
    • Structural data offers a foundation for designing novel immunomodulatory therapeutics.