Ligation of Cytotoxic T Lymphocyte Antigen-4 to T Cell Receptor Inhibits T Cell Activation and Directs Differentiation into Foxp3+ Regulatory T Cells

Background: Cross-linking of TCR to CTLA-4 attenuates TCR signaling and inhibits T activation. Results: A novel bispecific fusion protein comprising CD80 mutant (CD80w88a) and LAG-3 was designed to promote TCR and CTLA-4 cross-linking via MHCII. Conclusion: TCR and CTLA-4 cross-linking resulted in T cell inhibition and Foxp3(+) regulatory T cell differentiation. Significance: This novel bispecific protein may represent a new class of therapeutics for immune modulation.