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:
Moody DB, Young DC, Cheng T, Rosat J, Roura-mir C, O'connor, P, Zajonc, DM, Walz A, Miller MJ, Levery SB, Wilson IA, Costello CA and Brenner MB. T cell activation by lipopeptide antigens. Science 2004: 303, 527-530.
I Matsunaga, A Bhatt, DC Young, TY Cheng, GS Besra, S Porcelli, WR Jacobs, and DB Moody. Mycoketides: a novel polyketide synthesis pathway for antigenic lipids presented by CD1c. Journal of Experimental Medicine 2004; 200, p. 1559-1569.
DB Moody. TLR gateways to CD1 function. Nature Immunology 7, p. 8811 (2006).
Moody DB. Immunology: how a T cell sees sugar. Nature. 2007;448 (7149): 36-7.
Relloso M, Cheng TY, Im JS, Parisini E, Roura-Mir C, DeBono C, Zajonc DM, Murga LF, Ondrechen MJ, Wilson IA, Porcelli SA, Moody DB. pH-dependent interdomain tethers of CD1b regulate its antigen capture. Immunity. 2008;28(6):774-86. |
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