Conserved mycobacterial lipoglycoproteins activate TLR2 but also require glycosylation for MHC class II-restricted T cell activation.
CD4(+) T cell clones derived from a leprosy lesion and patient blood were used to monitor the isolation and identification of an Ag associated with the self-limited form of the disease. Biochemical purification and genetic analysis identified the T cell Ag as a conserved mycobacterial lipoglycoprotein LprG. LprG-mediated activation of CD4(+) T cells required specific MHC class II restriction molecules and intracellular processing. Although LprG activated TLR2, this alone was not sufficient to stimulate or inhibit T cell activation. A striking finding was that the carbohydrate moieties of LprG were required for optimal T cell activation, because recombinant LprG produced in Escherichia coli, or recombinant LprG produced in Mycobacterium smegmatis and digested by alpha-mannosidase, did not activate T cells. This study demonstrates that the universe of bacterial T cell Ags includes lipoglycoproteins, which act as TLR2 ligands but also require glycosylation for MHC class II-restricted T cell activation in vivo.
Sieling
Peter A
PA
Division of Dermatology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Hill
Preston J
PJ
Dobos
Karen M
KM
Brookman
Kerry
K
Kuhlman
Andrew M
AM
Fabri
Mario
M
Krutzik
Stephan R
SR
Rea
Thomas H
TH
Heaslip
Darragh G
DG
Belisle
John T
JT
Modlin
Robert L
RL
D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002241:Carbohydrates / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D043323:alpha-Mannosidase / Q000737:chemistry
D000942:Antigens, Bacterial; D002241:Carbohydrates; D000949:Histocompatibility Antigens Class II; D008074:Lipoproteins; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D043323:alpha-Mannosidase