Lipid Immunology10 months, 4 weeks ago
Posted on Feb 25, 2018, 7 p.m.
Insights from researchers at Monash University and Brigham into the basis for T cell receptor autoreactivity to self phospholipids hold implications for autoimmune diseases as published in Science Immunology.
Phospholipids are fat molecules that form the membranes around cells, and make up close to half of the dry weight of cells. But when it comes to autoimmune diseases the role of phospholipids has been overlooked and underappreciated. Research pointed in this direction has highlighted a role for phospholipids in numerous diseases including allergies, psoriasis, and contact hypersensitivities.
It is thought that certain autoimmune diseases such as type 1 diabetes, psoriasis, and multiple sclerosis are driven by particular tissues. Research for the particular molecules and antigens that may be the cause of the trigger for autoimmune diseases have been focused on peptides and proteins, leaving out lipids as a candidate antigen for autoimmune disease says Branch Moody, MD.
For at least several decades it has been know that hat T cells play a role in autoimmune disorders, but it was thought that T cells could respond to proteins only. T cells, are suggested by this study, to be able to respond to lipids, and highlights the physical structures that make recognition of lipids possible.
Activation of T cells occurs when dendritic cells present them with an antigen. The team designed this study in order to discover which molecules were involved, being captured and presented stimulating a T cell response. Structural biology was used to show how a protein on the surface of dendritic cells called CD1b binds to lipids, which then binds to a T cell receptor, activating an immune response. Advanced imaging facilities allowed the team to generate 3D models of the interactions. The researchers results point out the role of CD1b in phospholipid mediated immune response, which will help to develop a greater understanding of the mechanisms of lipid based autoimmune disease. The 3D images created by the team of how 3 different molecules interact serve to explain which part of the lipid matters, the knowledge of the precise structure of complexes involved in the interaction may be useful for designing new kinds of lipid that may possibly turn on or off the immune response.
Specific forms of autoimmune disease which includes systemic lupus erythematosus may benefit from this research. Patients with lupus have been shown to have antibodies that bind to phospholipids, which can cause strokes and clotting. T cells have been shown to have the ability to recognize phospholipids in this study, opening up new avenues for T cell and antibody research into this disease.