Multiple immune tolerance mechanisms prevent self-reactive T cells from becoming pathogenic. Autoimmunity occurs when these mechanisms break down. Thymic selection, also referred to as central tolerance, is the first prevention a self-reactive T cell encounters. During this process antigen recognizing T cell receptors (TCRs) are tested against various self-peptides, those that react too strongly are either deleted or shuttled into the regulatory T cell lineage. My research aims to understand how self-reactive T cells escape this process and initiate autoimmune disease.
One hypothesized method is through the expression of two different TCRs on a single T cells. An estimated 10-20% of all T cells express two functionally recombined TCRs. We hypothesize that this dual TCR expression can limit deletion and regulatory T cell commitment of strongly self-reactive T cells in the thymus. This could explain how self-reactive T cells escape the thymus and enter the periphery as pathogenic T cells. Dual TCR expression is hypothesized to play important roles in several other immune contexts including allo-responses in graft rejection, allergy, and protective immunity. We have developed new tools in our lab that allow us to detect and study dual TCR T cells in several immune contexts.
A second area of interest for the lab is neonatal immune development. At birth, the adaptive immune system is underdeveloped and may function differently than that of adults. As a result, infections are common in neonates and infants. The Schuldt Lab has begun a collaboration to investigate how early microbial exposure influences the development of adaptive immunity. Improved understanding of neonatal adaptive immunity could lead to improved vaccine platforms.
