• Ph.D., University of Chicago, 1989
• B.A., St. Olaf College, 1984

Research Interests: The research interests of my laboratory are on antigen recognition by T cells and how mutation of antigen can alter T cell activation. Antigen recognition is required for initiation of a T cell response, but the precise measure of this process remains to be elucidated. Clearly, the T cell receptor plays a critical role, yet beyond this general truth our understanding is quite limited. Ongoing projects in the lab seek to address the following questions. Does the interaction with a self-antigen that leads to autoimmunity differ in fundamental ways from recognition of epitopes presented from pathogens? How much TCR is needed to respond to antigen? Can one mutate the self-antigen mediating autoimmunity and ameliorate disease? What is the role of the SHP-1 tyrosine phosphatase in regulating overall activation levels of T cells? To address these problems, we make use of several model systems in which the antigenic peptide has been identified. By introducing mutations in the peptide sequence, we alter the interaction between peptide and major histocompatibility molecules, leading to a destabilization of the peptide:MHC ligand for T cells. Interestingly, we have found that destabilized peptide:MHC ligand leads to the induction of the tyrosine phosphatase SHP-1. This phosphatase appears to act as a negative regulator of T cell responses and dampens the overall extent of response. While we are currently testing our ideas using an animal model of multiple sclerosis called EAE, our studies will improve our overall understanding of T cell activation since unstable peptide:MHC complexes are widely observed in responses against self, tumors, and chronic infection.