Objective:

To investigate allosteric communication within antibodies and its effects on antigen-binding affinities across different classes and subclasses.

Approach:

• Methodology: Utilized surface plasmon resonance to compare IgA1, IgD, IgE, IgG1, IgG4, and IgM Fabs across five distinct antibody-antigen systems.
• Analysis: Conducted thermodynamic analysis to assess the influence of antibody flexibility and pre-organization on binding affinities.

Key Findings:

• Different CH1 domains produced varying allosteric differences in affinity.
• Larger long-range effects were observed from the Fc region to the Fab region.
• Full-length antibodies exhibited higher binding affinities than their Fab counterparts.

Interpretation:

Allosteric modulation of antigen binding, mediated by the CH1 domain, Fc region, and Fc-ligand interactions, is crucial for antibody function.

Limitations:

• The study primarily focused on five human antibody classes and may not represent all antibody interactions.
• Potential effects of avidity and molecular reach on affinity measurements were noted.

Conclusion:

The findings provide insights into the allosteric mechanisms influencing antibody function and may inform therapeutic antibody engineering.