Using humans as a model system, 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 endosomal compartments of dendritic ells and the roles of Toll-like receptors in promoting cellular antigen presentation. Through the Department of Medicine at the Brigham and Women’s hospital, we are using these lipids to study the function of CD1-restricted T cells in human patients with tuberculosis, autoimmune thyroiditis and drug hypersensitivity reactions. 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 molecules can be developed as immunomodulatory agents and vaccines for treatment of patients.
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Papers & Publications:
Cheng TY, Relloso M, Van Rhijn I, Young DC, Besra GS, Briken V, Zajonc DM, Wilson IA, Porcelli S, Moody DB. Role of lipid trimming and CD1 groove size in cellular antigen presentation. EMBO Journal. 2006;25(13):2989-99.
Moody DB. TLR gateways to CD1 function. Nature Immunology. 2006;7(8):811-7.
Moody DB, Zajonc DM, Wilson IA. Anatomy of CD1-lipid antigen complexes. Nature Reviews Immunology. 2005;5(5):387-99.
Moody DB, Young DC, Cheng TY, Rosat JP, Roura-Mir C, O'Connor PB, Zajonc DM, Walz A, Miller MJ, Levery SB, Wilson IA, Costello CE, Brenner MB. T cell activation by lipopeptide antigens. Science. 2004;303(5657):527-31.
Moody DB, Ulrichs T, Mühlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000;404(6780):884-8. |
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