Three-dimensional structure of an antigen-antibody complex at 6 A resolution

Area of Science:

• Structural Biology
• Immunology
• Biochemistry

Background:

• Current understanding of antibody combining sites relies on X-ray diffraction of immunoglobulins and their fragments complexed with small ligands.
• Limited crystallographic data exists for antigen-antibody complexes and the precise structure of protein antigenic determinants.

Purpose of the Study:

• To determine the three-dimensional structure of an antigen-antibody complex at high resolution.
• To elucidate the structural basis of antibody-antigen interactions and antigenic determinants.

Main Methods:

• X-ray diffraction studies were performed on a complex of hen egg-white lysozyme and the antigen-binding fragment (Fab) of a monoclonal anti-lysozyme antibody (D1.3).
• The structure was determined at 6 Angstrom resolution.

Main Results:

• The antibody combining site is a larger area extending beyond the complementarity-determining regions.
• A significant portion of the antigen engages in close contact with the antibody.
• The results support the concept of topographical antigenic determinants over sequential ones.

Conclusions:

• The determined structure provides a detailed model for understanding antibody-antigen interactions.
• This structural model facilitates visualization of antibody cross-reactivity and the impact of amino acid substitutions on specificity.