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David Branch Moody
Department of Rheumatology, Immunology and Allergy, Harvard University, Boston, United States of America

Faculty Member: IMMUNOLOGY > Antigen processing & recognition [ since 4 July 2001 ]
[ Biography ] [ Evaluations ]
Biography

Contact information
Smith 514
1 Jimmy Fund Way
Boston MA 02115
Fax 617-525-1010

My laboratory conducts basic research into the molecular and cellular mechanisms of immune recognition of glycolipid antigens. Recent studies of T cell responses to bacterial antigens have uncovered a previously unknown pathway for antigen presentation by a family of proteins known collectively as CD1. CD1 proteins are related to the major histocompatibility complex (MHC) class I and class II encoded antigen presenting molecules. However, unlike MHC class I and II that present peptide antigens, CD1 presents glycolipids for specific T cell recognition. We have identified a new family of the foreign glycolipids presented by CD1b to be glucose monomycolates and determined the specific molecular features of these antigens that activate an immune response (Moody, et al., Science 278, 283-8). Definition of the antigenic epitopes on these glycolipids clarifies the general molecular mechanism by which CD1 proteins present antigens to T cells. We have recently CD1c to be a family of isoprenoid glycolipids that is conserved throughout eukaryotes, including humans (Moody et al, Nature, 404, p.884). This expands the realm of targets of the human T cell response to include self glycolipids, suggesting a role of CD1 in autoimmunity and immunoregulation. Current studies are aimed at defining the molecular pathways by which mycobacteria synthesize glycosylated mycolates (Moody, et al., J Exp Med 192: 965-76), the cellular pathway by which glycolipids are taken up by cells, the molecular basis by which T cells discriminate self from foreign glycolipids (Moody et al., Immunol. Rev. 172, 285-296) and the role of microbial infection in controling dendritic cell maturation. The long term goal of these studies is to develop a detailed understanding of how the immune system specifically recognizes and responds to glycolipids and how these glycolipids function in the pathogenesis of infectious and autoimmune diseases.

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Evaluations

Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.
Jin MS, Kim SE, …, Lee H, Lee JO
Cell 2007 Sep 21 130(6):1071-82 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Clifford Harding / Rino Rappuoli / David Branch Moody
Evaluated 2 Apr 2008

CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor.
Borg NA, Wun KS, …, McCluskey J, Rossjohn J
Nature 2007 Jul 5 448(7149):44-9 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | David Branch Moody / Edward Collins / Toshinori Nakayama / Jia-huai Wang / Moriya Tsuji
Evaluated 3 Jul 2007

Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.
Kinjo Y, Tupin E, …, Wong CH, Kronenberg M
Nat Immunol 2006 Sep 7(9):978-86 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Dale Umetsu / David Branch Moody
Evaluated 2 Nov 2006

Toll-dependent selection of microbial antigens for presentation by dendritic cells.
Blander JM, Medzhitov R
Nature 2006 Apr 6 440(7085):808-12 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Christopher Karp / Torben Lund / Peter Van Endert / Elizabeth Mellins / David Branch Moody / Dan Conrad / Laurence Eisenlohr / Etienne Joly / Marcus Thelen / Victor Nizet
Evaluated 29 Mar 2006

Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family.
Miller MM, Wang C, …, Brenner MB, Dascher CC
Proc Natl Acad Sci U S A 2005 Jun 14 102(24):8674-9 [abstract on PubMed] [related articles] [FREE full text]
Selected by | David Branch Moody / Randy Brutkiewicz
Evaluated 18 Oct 2005

Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC.
Salomonsen J, Sørensen MR, …, Skjødt K, Kaufman J
Proc Natl Acad Sci U S A 2005 Jun 14 102(24):8668-73 [abstract on PubMed] [related articles] [FREE full text]
Selected by | Stephan Beck / David Branch Moody / Randy Brutkiewicz
Evaluated 11 Oct 2005

Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins.
Zenz R, Eferl R, …, Tschachler E, Wagner EF
Nature 2005 Sep 15 437(7057):369-75 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | David Branch Moody / Luciano Adorini
Evaluated 6 Oct 2005


Recognition of bacterial glycosphingolipids by natural killer T cells.
Kinjo Y, Wu D, …, Wong CH, Kronenberg M
Nature 2005 Mar 24 434(7032):520-5 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Eric Vivier / David Branch Moody
Evaluated 18 Apr 2005

Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.
Mattner J, Debord KL, …, Savage PB, Bendelac A
Nature 2005 Mar 24 434(7032):525-9 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Eric Vivier / Richard Locksley / David Branch Moody
Evaluated 18 Apr 2005

Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins.
Zhou D, Cantu C, …, Bendelac A, Teyton L
Science 2004 Jan 23 303(5657):523-7 [abstract on PubMed] [related articles] [FREE full text]
Selected by | Yutaka Tagaya / David Branch Moody
Evaluated 29 Mar 2004

Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice.
Sakaguchi N, Takahashi T, …, Nakatsuru S, Sakaguchi S
Nature 2003 Nov 27 426(6965):454-60 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Torben Lund / Paul Lyons / Andy Chan / David Branch Moody
Evaluated 29 Mar 2004

Human CD8+ T cells store RANTES in a unique secretory compartment and release it rapidly after TcR stimulation.
Catalfamo M, Karpova T, …, Peters PJ, Henkart PA
Immunity 2004 Feb 20(2):219-30 [abstract on PubMed] [related articles] [order article]
Selected by | Eric Denkers / Yutaka Tagaya / David Branch Moody
Evaluated 29 Mar 2004

Molecular identification of a danger signal that alerts the immune system to dying cells.
Shi Y, Evans JE, Rock KL
Nature 2003 Oct 2 425(6957):516-21 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | Caetano Reis e Sousa / Allan Zajac / Jonathan Gleadle / Michael Gold / Michael McHeyzer-Williams / David Branch Moody / Stefan Kaufmann / Matthias von Herrath / Luis J. Montaner / Richard Vile
Evaluated 23 Oct 2003

Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance.
Probst HC, Lagnel J, Kollias G, van den Broek M
Immunity 2003 May 18(5):713-20 [abstract on PubMed] [related articles] [order article]
Selected by | David Gray / David Branch Moody
Evaluated 26 Jun 2003

Activation of lysosomal function during dendritic cell maturation.
Trombetta ES, Ebersold M, …, Pypaert M, Mellman I
Science 2003 Feb 28 299(5611):1400-3 [abstract on PubMed] [related articles] [FREE full text]
Selected by | Peter Jensen / Sergio Grinstein / David Branch Moody
Evaluated 19 Mar 2003

Helper T cells regulate type-2 innate immunity in vivo.
Shinkai K, Mohrs M, Locksley RM
Nature 2002 Dec 19-26 420(6917):825-9 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | David Chaplin / Stefan Kaufmann / David Branch Moody
Evaluated 17 Jan 2003

Structure of human CD1b with bound ligands at 2.3 A, a maze for alkyl chains.
Gadola SD, Zaccai NR, …, Jones EY, Cerundolo V
Nat Immunol 2002 Aug 3(8):721-6 [abstract on PubMed] [related articles] [full text] [order article]
Selected by | David Branch Moody
Evaluated 6 Aug 2002

Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells.
Roberts TJ, Sriram V, …, Yewdell JW, Brutkiewicz RR
J Immunol 2002 Jun 1 168(11):5409-14 [abstract on PubMed] [related articles] [FREE full text]
Selected by | David Branch Moody
Evaluated 6 Jun 2002

Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells.
Gilliet M, Liu YJ
J Exp Med 2002 Mar 18 195(6):695-704 [abstract on PubMed] [related articles] [FREE full text]
Selected by | David Branch Moody
Evaluated 3 May 2002

Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus.
Blanco P, Palucka AK, …, Pascual V, Banchereau J
Science 2001 Nov 16 294(5546):1540-3 [abstract on PubMed] [related articles] [FREE full text]
Selected by | Andy Chan / Peter Jensen / David Branch Moody
Evaluated 12 Mar 2002

CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain.
Jayawardena-Wolf J, Benlagha K, …, Mehr R, Bendelac A
Immunity 2001 Dec 15(6):897-908 [abstract on PubMed] [related articles] [order article]
Selected by | David Branch Moody / Alexander Rudensky
Evaluated 22 Jan 2002

Involvement of cellular caveolae in bacterial entry into mast cells.
Shin JS, Gao Z, Abraham SN
Science 2000 Aug 4 289(5480):785-8 [abstract on PubMed] [related articles] [FREE full text]
Selected by | David Branch Moody
Evaluated 9 Oct 2001

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