Investigator Asst Prof (M) Center for Immunology and Inflammatory Diseases, Mass General Research Institute

Assistant Professor of Medicine Harvard Medical School

autoantigens; cd4-positive t-lymphocytes; epitopes, t-lymphocyte; forkhead transcription factors; histocompatibility antigens; histocompatibility antigens class ii; immunity, cellular; peptides; precursor cells, t-lymphoid; receptors, antigen, t-cell; salmonella; salmonella infections, animal; typhoid fever CD4+ T lymphocytes comprise a principal component of the adaptive immune system. These cells recognize protein-derived antigens from foreign pathogens and integrate this information with contextual signals to coordinate appropriately orchestrated responses from all the different players of the immune system, including cytotoxic CD8+ T cells, antibody-producing B cells, and inflammatory macrophages and granulocytes. The role of CD4+ T cells as central regulators of immune function therefore makes them an attractive target for immunoregulatory intervention when immune responses go awry.

The overall research goal of the Moon Laboratory is to understand how CD4+ T cell tolerance is maintained to antigens that should not be attacked by the immune system. This includes not only self-antigens, but antigens derived from commensal microbes and environmental proteins that continuously or routinely make contact with mucosal surfaces. Undesirable immune responses to these types of antigens are the underlying causes of autoimmune, autoinflammatory, and allergic diseases, respectively.

Our aim is to understand the extent to which deletional tolerance is established for CD4+ T cells with specificity to such antigens, and what overlapping roles various peripheral mechanisms of tolerance play in suppressing these T cells in a steady state manner. Our lab designs and utilizes state-of-the-art peptide:MHC multimer reagents in conjunction with a variety of cellular, molecular, and genetic approaches to study CD4+ T cell tolerance in vivo in both mouse and human experimental systems. The achievement of our goals will provide a stronger foundation for understanding the initiation and progression of hyperimmune diseases and lead to the development of new therapies to treat them.