Characterization of the Antigenic Heterogeneity of Lipoarabinomannan, the Major Surface Glycolipid of Mycobacterium tuberculosis, and Complexity of Antibody Specificities toward This Antigen.

摘要: Lipoarabinomannan (LAM), the major antigenic glycolipid of Mycobacterium tuberculosis , is an important immunodiagnostic target for detecting (TB) infection in HIV-1–coinfected patients, and believed to mediate a number functions that promote disease development. To probe human humoral response against LAM during TB infection, several novel LAM-specific mAbs were molecularly cloned from memory B cells isolated infected patients grown vitro. The fine epitope specificities these Abs, along with those panel previously described murine phage-derived mAbs, mapped using binding assays Ags mycobacterial species synthetic glycans glycoconjugates represented diverse carbohydrate structures present LAM. Multiple reactivity patterns seen differed their specificity different species, as well dependence on arabinofuranoside branching nature capping at nonreducing termini. Competition studies soluble further defined guided design highly sensitive immunodetection capable urine even absence HIV-1 coinfection. These results highlighted complexity structure diversity natural Ab this target. information reagents study will allow optimization diagnostic may facilitate development potential immunotherapeutic approaches inhibit functional activities specific structural motifs