For years, scientists believed antibodies couldn’t safely target lipids without attacking healthy cells. These fatty molecules are widespread throughout the body. However, researchers at Scripps Research have now shown how a special class of antibodies uses lipids to recognize the HIV virus—a finding that could advance vaccine development and autoimmune research.
Modeling Antibody-Lipid Interactions
Using computer simulations, the team studied broadly neutralizing antibodies (bNAbs) that bind to the membrane-proximal external region (MPER) of HIV—an elusive site embedded in the viral membrane. The simulations revealed that loop regions, known for their adaptability, and framework regions, once thought unimportant, both play critical roles in recognizing the virus.
“These simulations give us a blueprint for vaccine design,” said Marco Mravic, assistant professor at Scripps.
Simulations Mirror Nature’s Accuracy
Lead author Colleen Maillie was surprised at how precisely the models reproduced real-world interactions. By simulating antibodies in a pure lipid bilayer, the team discovered that antibodies likely target the lipid membrane first, then move to the MPER.
Antibodies Mature with Lipid Specificity
Interestingly, as antibodies matured, their affinity for HIV’s lipid membrane increased—a trait previously linked with autoimmune diseases. However, these bNAbs showed highly specific lipid targeting, possibly avoiding harmful self-recognition.
Implications Beyond HIV
As reported by medicalxpress, the findings could help design antibodies for other membrane-associated diseases, such as lupus. They may also support synthetic antibody engineering for drug development.
The study, titled “Ab initio prediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations”.