Mycobacterium tuberculosis H37Rv parietal and cellular lipoarabinomannans. Characterization of the acyl- and glyco-forms.
Mannosylated lipoarabinomannans are multifaceted molecules. They have been shown to exert an immunosuppressive role in the immunopathogenesis of tuberculosis. They are also described as antigens of host double negative alphabeta T-cells. Delimitation of ManLAMs epitopes require knowledge of the precise structure of these molecules. The two major functional domains (the cap motifs and the phosphatidylinositol anchor) of the parietal and cellular ManLAMs of Mycobacterium tuberculosis H37Rv were investigated here. Using capillary electrophoresis, we established that parietal and cellular ManLAMs share the same capping motifs, mono-, di-, and trimannosyl units with the same relative abundance. By (31)P NMR analysis of the native LAMs in Me(2)SO-d(6), the major acyl-form of both parietal and cellular H37Rv ManLAM anchors, typified by the P3 phosphorus resonance, comprised a diacylglycerol unit. Three other acyl-forms were characterized in the cellular ManLAMs. Comparative analysis of the cellular Mycobacterium bovis BCG and M. tuberculosis ManLAM acyl-forms revealed the presence of the same populations, but with different relative abundance. The biological importance of the H37Rv ManLAM acyl-form characterization is discussed, particularly concerning the molecular mechanisms of binding of ManLAMs to the CD1 proteins involved in the presentation of ManLAMs to T-cell receptors.
Gilleron
M
M
Institut de Pharmacologie et de Biologie Structurale du Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077 Toulouse Cedex, France. gilleron@ipbs.fr
Bala
L
L
Brando
T
T
Vercellone
A
A
Puzo
G
G
D000215:Acylation; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000737:chemistry; D018949:Antigens, CD1; D002240:Carbohydrate Sequence; D019075:Electrophoresis, Capillary; D017261:Glycosylphosphatidylinositols; D008070:Lipopolysaccharides / Q000737:chemistry*; D008351:Mannans / Q000737:chemistry*; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D017261:Glycosylphosphatidylinositols; D008070:Lipopolysaccharides; D008351:Mannans; C050016:lipoarabinomannan