New Method Enhances Antibody Generation for Protein Complexes

Scientists have developed a novel approach to generate monoclonal antibodies for protein complexes, potentially opening new avenues for disease research and treatment. A study published in the Journal of Immunology, by researchers from Sanford Burnham Prebys and Eli Lilly, demonstrates that fusing protein complexes together can overcome limitations in traditional antibody production methods.

The research focused on two proteins found on immune cells: B and T lymphocyte attenuator (BTLA) and herpesvirus entry mediator (HVEM). These proteins form a complex that influences immune system responses and may play a role in diseases such as lupus. However, measuring the ratio of freestanding proteins to their combined form has been challenging due to the instability of protein complexes during the conventional immunization process.

To address this issue, the team created a fusion protein based on the BTLA-HVEM complex. This increased stability allowed for successful generation of monoclonal antibodies. The researchers then identified the most effective antibody for binding to the fusion protein and used it to compare amounts of freestanding BTLA and HVEM with their protein complex in various immune cells.

"Our study is the first to demonstrate this direct measurement on live cells using a complex-specific monoclonal antibody," explained senior author Carl Ware. He added that these findings could aid in diagnosing or monitoring lupus and certain cancers with HVEM mutations.

The study suggests that this fusion protein approach may have broader applications in studying other disease-related protein complexes and potentially developing new treatments. As the global market for antibodies in clinical care and research continues to expand, this method could unlock new opportunities for antibody generation and disease research.