Dr. Maria Bettini's research interests are in the area of autoimmune diabetes, with specific focus on T cells and the T cell receptor (TCR) role in autoimmune disease development. Current projects are focused on how T cell receptor affinity controls activation of tolerogenic and regulatory pathways that restrain autoimmune activation. Specifically, we are interested in self-antigen reactive Foxp3+ Treg cells that accumulate in the pancreas during islet infiltration and to some degree protect the beta cells from final destruction. Our main goal is to identify TCR affinities and specificities that promote Treg development, proliferation, survival and stability during progression to autoimmune disease. We hope to utilize this knowledge for development of immunotherapies for T1D treatment and prevention.
Our expertise utilizing the in vivo TCR retrogenic system along with a panel of TCRs specific for the dominant insulin epitope, in vivo humanized systems, together with TCRs isolated from human patients, provide an exciting opportunity to dissect the mechanisms of T cell pathogenicity and tolerance in type 1 diabetes. We are undertaking a multidisciplinary and collaborative approach to reach the following goals: (1) determine the role of TCR affinity in T cell pathogenicity, tolerance and T cell population dynamics in type 1 diabetes; (2) investigate how TCR affinity dictates autoreactive T cell responses to tolerogenic therapies; (3) determine the role of tolerance mechanisms in regulating the pathogenic potential of human T cells specific for the natural or post-translationally modified beta cell antigens. Together, the results of these studies will have a broad impact on our understanding of T cell responses in autoimmune diseases with potential implications for other chronic inflammatory conditions.