The Moody laboratory seeks to understand how human T cells control outcomes of infection and autoimmune disease. CD1 proteins are a family of evolutionarily conserved antigen presenting molecules that bind lipid antigens for presentation to T cells. Using mass spectrometry to study the lipid content of the cell wall of M. tuberculosis, we have discovered of lipid ligands for CD1a, CD1b, CD1c and CD1d proteins. Using these model antigens, we are studying the cellular mechanisms of lipid loading onto CD1 proteins in dendritic cells and the roles of Toll-like receptors in promoting cellular antigen presentation. Recently, we have reported the first studies of CD1a, CD1b and CD1c tetramers in humans. Through the Department of Medicine at the Brigham and Women’s hospital, we are using these lipids and tetramers to study the function of CD1-restricted T cells in healthy humans and in disease states. Recent studies have identified new populations of human T cells, including IL-22 secreting CD1a autoreactive T cells and germline encoded mycolyl reactive (GEM) T cells. Further, we have reported new mechanisms of T cell recognition of self lipids whereby TCRs take unexpected binding positions on CD1 lipid complexes. Last, we have developed a program to identify the molecular mechanisms of virulence by the pathogen M. tuberculosis. This program had uncovered mechanisms by which this intracellular pathogen remodels its growth niche in macrophages, converting phagolysosomes from killing compartments into lipid-rich feeding compartments. Our overall goal is to develop a basic understanding of the cellular mechanisms that allow T cells to discriminate among self and foreign antigens, so that these antigens and adjuvants can be developed as immunomodulatory agents and vaccines for treatment of patients.