A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components

摘要: γ9δ2 T cells provide a natural bridge between innate and adaptive immunity, rapidly potently respond to pathogen infection in mucosal tissues, are prominently induced by both tuberculosis (TB) bacillus Calmette Guerin (BCG) vaccination. Mycobacterium-expanded represent only subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive cells, expressing an oligoclonal set cell receptor (TCR) sequences which more efficiently recognize inhibit intracellular Mycobacterium infection. Based on this premise, we have been searching for M. antigens specifically capable inducing unique mycobacterium-protective cells. Our screening strategy includes identification fractions that expand with biological functions inhibiting mycobacterial replication. Chemical treatments whole-cell lysates (MtbWL) ruled out protein, nucleic acid, nonpolar lipids as protective Mild acid hydrolysis, transforms complex carbohydrate monomeric residues, abrogated specific activity lysates, suggesting polysaccharide was required activity. Extraction MtbWL chloroform-methanol-water (10:10:3) resulted polar lipid fraction highly enriched activity; further silica gel chromatography. A combination mass spectrometry nuclear magnetic resonance analysis bioactive indicated 6-O-methylglucose-containing lipopolysaccharides (mGLP) predominant components present active fraction. These results important implications development new immunotherapeutic approaches prevention treatment TB.