Instructor

Cancer Immunology and AIDS

Department of Pathology, Harvard Medical School

Dana-Farber Cancer Institute (Boston, MA)

Kai W Wucherpfennig

Enhancing peptide presentation by MHC class II with small molecules

The MHC class II pathway is dedicated to the processing and presentation of exogenously derived protein antigens in a form that is recognizable to the cells of the adaptive immune system. Under normal conditions, the MHC class II-peptide repertoire presented at the surface of an Antigen Presenting Cell represents a stable sampling of peptides derived from the regular turnover of self proteins. However, during active infection or other physical insult, the MHC class II-peptide repertoire can be rapidly altered to reflect the presence of extracellular pathogens, transformed cells or other foreign antigens and initiate an adaptive immune response. The focus of my research is to understand the mechanism and manipulate the outcome of peptide binding by MHC class II molecules. Through high-throughput screening efforts we have found a number of small molecules that enhance peptide binding to MHC class II. One class of small molecules is able to mimic the function of DM, the protein that catalyzes peptide exchange in vivo.