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 tuber culosis. They are also described as antigens of host double negative alpha beta T-cells, Delimitation of ManLAMs epitopes require knowledge of the pre cise structure of these molecules, The two major functional domains (the ca p motifs and the phosphatidylinositol anchor) of the parietal and cellular ManLAMs of Mycobacterium tuberculosis H37Rv were investigated here. Using c apillary electrophoresis, we established that parietal and cellular ManLAMs share the same capping motifs, mono-, di-, and trimannosyl units with the same relative abundance. By P-31 NMR analysis of the native LAMs in Me2SO-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, Compara tive analysis of the cellular Mycobacterium bovis BCG and M. tuberculosis M anLAM acyl-forms revealed the presence of the same populations, but with di fferent relative abundance. The biological importance of the H37Rv ManLAM a cyl-form characterization is discussed, particularly concerning the molecul ar mechanisms of binding of ManLAMs to the CD1 proteins involved in the pre sentation of ManLAMs to T-cell receptors.