Investigating peripheral T cell tolerance
REgulation of self-antigen-specific T cell Responses
Peripheral tolerance is the prevention and turning-off of aberrant T cell responses against self-antigens. The mechanisms for these processes remain very unclear in vivo, in part because of the powerful role of central tolerance in preventing auto-reactive T cells from escaping into the periphery. Thus, it has been difficult to study how natural peripheral tolerance arises and is maintained. Most studies have focused on the critical need for costimulatory molecules to “break” self tolerance, but the recent emergence of adverse events following immune checkpoint therapy is challenging this notion and pointing to an essential role for inhibitory receptors in maintaining self-tolerance. Our team is using genetically engineered models that bypass central tolerance and allow us to induce self-antigen expression in the periphery to investigate these mechanisms to tolerance and how their breakdown leads to disease.
This work is funded by a grant from the Mather’s Foundation.