Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• CD2 and CD58 (LFA-3) interactions are vital for immune cell recognition and contact.
• These interactions facilitate communication between T lymphocytes and antigen-presenting cells, as well as effector and target cells.

Purpose of the Study:

• To determine the crystal structure of the heterophilic adhesion complex between human CD2 and CD58 amino-terminal domains.
• To elucidate the molecular basis of CD2-CD58 binding specificity and affinity.

Main Methods:

• X-ray crystallography was used to determine the three-dimensional structure of the CD2-CD58 complex.
• Analysis of the protein-protein interface to identify key interactions and assess complementarity.

Main Results:

• The structure reveals a strikingly asymmetric, orthogonal, face-to-face interaction between the immunoglobulin-like domains of CD2 and CD58.
• The interface, lacking significant hydrophobic forces, is dominated by interdigitating charged amino acid side chains forming hydrogen bonds and salt links.
• This interaction exhibits poor shape complementarity but high specificity, with low affinity (K(D) in the microM range).

Conclusions:

• The unique binding mode explains the dynamic nature of CD2-CD58 interactions in immune responses.
• These findings provide insights into the binding mechanisms of related immunoglobulin superfamily receptors.
• Understanding this interaction is crucial for comprehending immune cell adhesion and activation processes.