Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Antigen Presentation / immunology*
-
Antigens, Bacterial / immunology*
-
Apoptosis / immunology
-
Bacterial Proteins / immunology*
-
Blotting, Western
-
CHO Cells
-
Cell Wall / chemistry
-
Cell Wall / immunology
-
Cells, Cultured
-
Cricetinae
-
Cricetulus
-
Enzyme-Linked Immunosorbent Assay
-
Histocompatibility Antigens Class II / immunology*
-
Humans
-
In Situ Nick-End Labeling
-
Ligands
-
Lipoproteins / immunology
-
Macrophages / immunology*
-
Mass Spectrometry
-
Membrane Glycoproteins / immunology*
-
Molecular Sequence Data
-
Receptors, Cell Surface / immunology*
-
Sequence Analysis, Protein
-
Toll-Like Receptor 2
-
Toll-Like Receptors
-
Tumor Necrosis Factor-alpha / immunology
Substances
-
Antigens, Bacterial
-
Bacterial Proteins
-
Histocompatibility Antigens Class II
-
Ligands
-
Lipoproteins
-
Membrane Glycoproteins
-
Receptors, Cell Surface
-
TLR2 protein, human
-
Toll-Like Receptor 2
-
Toll-Like Receptors
-
Tumor Necrosis Factor-alpha
-
Mycobacterium tuberculosis antigens