Mycobacterium tuberculosis LprG (Rv1411c): a novel TLR-2 ligand that inhibits human macrophage class II MHC antigen processing.
MHC class II (MHC-II)-restricted CD4(+) T cells are essential for control of Mycobacterium tuberculosis infection. This report describes the identification and purification of LprG (Rv1411c) as an inhibitor of primary human macrophage MHC-II Ag processing. LprG is a 24-kDa lipoprotein found in the M. tuberculosis cell wall. Prolonged exposure (>16 h) of human macrophages to LprG resulted in marked inhibition of MHC-II Ag processing. Inhibition of MHC-II Ag processing was dependent on TLR-2. Short-term exposure (<6 h) to LprG stimulated TLR-2-dependent TNF-alpha production. Thus, LprG can exploit TLR-2 signaling to inhibit MHC-II Ag processing in human macrophages. Inhibition of MHC-II Ag processing by mycobacterial lipoproteins may allow M. tuberculosis, within infected macrophages, to avoid recognition by CD4(+) T cells.
Gehring
Adam J
AJ
Division of Infectious Diseases, Case Western Reserve University and University Hospitals of Cleveland, OH 44106, USA.
Dobos
Karen M
KM
Belisle
John T
JT
Harding
Clifford V
CV
Boom
W Henry
WH
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D015153:Blotting, Western; D016466:CHO Cells; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008074:Lipoproteins / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000276:immunology*; D020539:Sequence Analysis, Protein; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C072681:Mycobacterium tuberculosis antigens