D. Branch Moody
Brigham and Women's Hospital
Smith Bldg., Rm. 514
One Jimmy Fund Way
Boston, MA 2115
We conduct basic research into the cellular mechanisms by which CD1 proteins, MHC class II proteins and Toll-like receptors control T cell activation. 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 ells 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 normal humans and 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. 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 lipid antigens and adjuvants can be developed as immunomodulatory agents and vaccines for treatment of patients.
de Jong A et al. CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire. Nature Immunology, 2010.
Yakimchuk K., et al. Borrelia burgdorferi infection regulates CD1 expression in human cells and tissues via IL1-β. Eur J Immunol 2011.
Kasmar AG, et al. CD1b tetramers bind αβ T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans. J Exp Med 2011.
Huang S et al. Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system. PNAS 2011.
Ly D, et al. CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. J Exp Med. 2013.
Van Rhijn I, et al. A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nature Immunology 2013.
Last Update: 1/6/2014