HLA-DM co-expression enhances MHC class II function in the magnetosome display system

Area of Science:

• Biotechnology
• Immunology
• Microbial Engineering

Background:

• Efficient identification of antigenic peptides binding to MHC II is vital for vaccine and therapeutic development.
• Mammalian expression systems face limitations in cost and scalability for stable peptide exchange.
• High-throughput screening of MHC II-peptide interactions is a bottleneck in antigen discovery.

Purpose of the Study:

• To develop a bacterial magnetosome surface display system for co-expressing MHC II and HLA-DM.
• To enhance MHC II stabilization, immobilization, and functional peptide loading.
• To provide a scalable and cost-effective alternative to mammalian expression systems for antigen discovery.

Main Methods:

• Utilized *Magnetospirillum magneticum* to create a magnetosome surface display system.
• Co-expressed MHC II and HLA-DM on magnetosome surfaces using cohesin-dockerin interactions.
• Assessed peptide loading efficiency using an influenza-derived epitope (HA₃₀₆-₃₁₈).

Main Results:

• Achieved spatial co-localization of MHC II and HLA-DM on magnetosomes, enhancing stabilization and immobilization.
• Demonstrated improved functional MHC II peptide loading and binding affinity.
• Provided structural insights into HLA-DM's role in stabilizing MHC II and facilitating peptide loading.

Conclusions:

• The bacterial magnetosome system offers a robust platform for high-throughput antigen discovery.
• This system enhances functional peptide loading and stability, overcoming limitations of mammalian systems.
• It represents a promising tool for rational vaccine design and immunotherapy development.