The human adaptive immune system serves as the primary defense against a host of pathogenic bacteria, viruses, and fungi. At the heart of the adaptive immune response are the Major Histocompatibility Complex II (MHCII) molecules, which initiate the immune response against infection. The expression of the MHCII molecules is tightly regulated by a cell-specific multi-protein complex termed the MHCII enhanceosome. The heterotrimeric RFX complex is the key DNA binding component of the MHCII enhanceosome. Mutations or deletions in the three RFX proteins that disrupt formation of the RFX complex prevent the expression of MHCII genes and give rise to a severe immunodeficiency disease. The RFX complex is unique to the MHCII enhanceosome and therefore is a potential structural target for rational drug design of immunosuppressants. Such drugs would find use in treating autoimmune disease and preventing organ transplant rejection.

The overall aim of our research is to develop a model of the MHCII enhanceosome. To achieve this we are using X-ray crystallography, NMR, static light scattering, chemical crosslinking, and a variety of other biophysical methods. Our current focus is on the heterotrimeric RFX complex and how it interacts with DNA.