There are two distinct layers of cellular heterogeneity in the adaptive immune system; one is genetic- the enormous diversity of lymphocyte antigen receptor genes, while the other is non-genetic- the diverse functional phenotypes that lymphocytes can adopt. These two layers must be appropriately coupled so that each lymphocyte acquires and exerts an effector function tailored to the specific antigen it recognizes and protects our body from various diseases including infectious diseases, cancer, allergy, and autoimmune diseases. How appropriate coupling between the genetic and non-genetic heterogeneity is achieved and whether and how dysregulated coupling leads to diseases represent fundamental biological questions. The goal of this project is to address these questions by establishing a new method that allows us to measure both T cell receptor (TCR) sequences and functional phenotypes in T cell populations at the single cell level.
Uncovering genetic and non-genetic heterogeneity in T lymphocyte populations in health and disease
RIKEN Center for Integrative Medical Sciences
Laboratory for Immune Homeostasis