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Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2

G F Gao1, J Tormo, U C Gerth

  • 1Molecular Immunology Group, Nuffield Department of Clinical Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.

Nature
|June 5, 1997
PubMed

Insights

The CD8 glycoprotein binds to MHC class I molecules, stabilizing T-cell interactions. Crystal structure reveals CD8alpha(alpha) binding to HLA-A2, influencing T-cell receptor recognition.

Area of Science:

  • Immunology
  • Structural Biology
  • Biochemistry

Background:

  • CD8 glycoprotein is essential for cytotoxic T cell selection.
  • CD8 (homodimer CD8alpha(alpha) or heterodimer CD8alpha beta) stabilizes T-cell receptor (TCR) interactions with MHC class I/peptide complexes.
  • CD8 binding to MHC class I molecules enhances TCR recognition.

Purpose of the Study:

  • To determine the crystal structure of the CD8alpha(alpha) and human MHC molecule HLA-A2 complex.
  • To elucidate the molecular interactions between CD8alpha(alpha) and HLA-A2/peptide.
  • To understand how CD8 binding affects TCR-peptide-MHC interactions.

Main Methods:

  • X-ray crystallography at 2.7 A resolution.
  • Structural analysis of the CD8alpha(alpha)-HLA-A2/peptide complex.

Main Results:

  • The crystal structure reveals CD8alpha(alpha) binds to a single HLA-A2/peptide molecule.
  • CD8alpha(alpha) interfaces with HLA-A2's alpha2 and alpha3 domains and contacts beta2-microglobulin.
  • A flexible loop in the HLA-A2 alpha3 domain is clamped by CD8 subunits, preventing secondary MHC binding and altering alpha3 domain positioning.
  • These structural changes modulate affinity but do not alter the MHC/peptide surface for TCR recognition.

Conclusions:

  • CD8 binding to MHC class I involves specific structural interactions.
  • The CD8-MHC interaction contributes to avidity in TCR-peptide-MHC recognition.
  • Structural insights provide a basis for understanding T cell activation and immune response.

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