Food Antigen Atlas for New Regulatory T Cell Therapies in Food Allergy
Funded by Food Allergy Fund
Dr. Alexander Marson and Dr. Michael Fischbach as Principal Investigators
Building on its recent advances with the Chan Zuckerberg Biohub Billion Cells Project, “a project (which) will provide a necessary scale of data to understand the functional effects of human genetic variants and characterize the genetic drivers of human disease,” the Marson Lab at UCSF and the Gladstone Institutes and the Fishbach Group at Stanford University will now partner to build a T Cell Receptor (TCR) atlas based on immune derived overreactions to harmless food proteins. A key part of the immune response involves T cells, which can either drive allergic reactions (inflammatory T helper 2 cells) or help prevent them and maintain tolerance (regulatory T cells). Each T cell uses a unique receptor, or TCR, that can inappropriately recognize small fragments of food proteins (peptides) displayed by other cells. Understanding exactly which food fragments are recognized by which T cells is essential for developing better diagnostics and long-lasting treatments. However, this has been difficult to study systematically given the staggering diversity of both possible food antigens and unique TCRs that recognize these antigens. To overcome this challenge, we will apply two complementary technologies to identify specific food antigens of previously uncharacterized (“orphan”) T cell receptors from food allergic patients and understand how these immune responses develop. Our first platform, recently developed in collaboration with several other labs, uses barcoded, peptide-coated particles to directly link individual TCRs to the antigens they recognize, enabling high-throughput and simultaneous mapping of thousands of interactions between TCRs and antigens in a single experiment. Our second platform screens panels of identified TCRs against a broad panel of food ingredients to then zero in on a specific antigen. Ultimately, our project aims to translate these discoveries into new therapies by reprogramming regulatory T cells (Tregs) to suppress allergic reactions. By building a comprehensive atlas of food allergens and their immune interactions, this work could pave the way for more precise diagnostics and personalized treatments, improving the lives of people with food allergies.
