Structural Immunology

Elucidating the Basic Principles of Self vs Non-self RNA Discrimination by the Immune System

The ability to distinguish “self” from “non-self” is fundamental to proper functioning of both the innate and adaptive immune systems. Several pattern recognition receptors (PRR) in the innate immune system are responsible for the initial detection of foreign molecules associated with pathogens such as bacterial cell wall components or viral nucleic acids. We are particularly interested in how PRRs efficiently and accurately discriminate between self and non-self RNAs that are made up of identical building blocks. It was traditionally believed that dsRNA structures, which are often present in viral RNAs, provide sufficient means for PRRs to selectively recognize viral RNAs against the background of cellular RNAs. However, accumulating evidence suggests that the mechanism for viral RNA detection is more complex than a simple duplex binding, and understanding the molecular mechanism would require more detailed structural and biochemical dissection at the level of both ligand-receptor as well as receptor-signaling adaptor interactions. Our lab uses a combination of crystallography, computational modeling and a variety of biochemical and biophysical methods to determine the structures, dynamics and functions of these receptors in isolation, in complex with RNAs and in higher order complexes with functional partners in the signaling pathway.