T cell activation by lipopeptide antigens.
Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.
Moody
D Branch
DB
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Smith Building Room 514, 1 Jimmy Fund Way, Boston, MA 02115, USA. bmoody@rics.bwh.harvard.edu
Young
David C
DC
Cheng
Tan-Yun
TY
Rosat
Jean-Pierre
JP
Roura-Mir
Carme
C
O'Connor
Peter B
PB
Zajonc
Dirk M
DM
Walz
Andrew
A
Miller
Marvin J
MJ
Levery
Steven B
SB
Wilson
Ian A
IA
Costello
Catherine E
CE
Brenner
Michael B
MB
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D006900:Hydroxylation; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D010080:Oxazoles / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000942:Antigens, Bacterial; D018949:Antigens, CD1; C419393:CD1a antigen; D008074:Lipoproteins; D010080:Oxazoles; D016693:Receptors, Antigen, T-Cell, alpha-beta; C018608:mycobactins