Abstract
The surface polysacharide arabinomannan (AM) and related glycolipid lipoarabinomannan (LAM) play critical roles in tuberculosis pathogenesis. Human antibody responses to AM/LAM are heterogenous and knowledge of reactivity to specific glycan epitopes at the monoclonal level is limited, especially in individuals who can control M. tuberculosis infection. We generated human IgG mAbs to AM/LAM from B cells of two asymptomatic individuals exposed to or latently infected with M. tuberculosis. Here, we show that two of these mAbs have high affinity to AM/LAM, are non-competing, and recognize different glycan epitopes distinct from other anti-AM/LAM mAbs reported. Both mAbs recognize virulent M. tuberculosis and nontuberculous mycobacteria with marked differences, can be used for the detection of urinary LAM, and can detect M. tuberculosis and LAM in infected lungs. These mAbs enhance our understanding of the spectrum of antibodies to AM/LAM epitopes in humans and are valuable for tuberculosis diagnostic and research applications.
Highlights
The surface polysacharide arabinomannan (AM) and related glycolipid lipoarabinomannan (LAM) play critical roles in tuberculosis pathogenesis
There is a resurgence of interest in the generation of monoclonal antibodies to the mycobacterial cell wall glycolipid lipoarabinomannan (LAM) to improve the limited sensitivity of currently available urinary LAM (U-LAM) detection tests for the diagnosis of TB
Subjects T1 and L1 were selected for single B cell sorting and antibody generation based on availability of peripheral blood mononuclear cells (PBMC), high serum anti-AM immunoglobulin G (IgG) titers, and protective polyclonal anti-AM IgG functions against Mycobacterium tuberculosis (Mtb)[15]
Summary
The surface polysacharide arabinomannan (AM) and related glycolipid lipoarabinomannan (LAM) play critical roles in tuberculosis pathogenesis. While an estimated quarter of the world is latently infected with Mtb[2], TB is caused by uncontrolled infection leading to a predominantly respiratory and transmissible disease To combat this major global public health problem, better vaccines, therapies, and additional tools for both diagnosis and research are critical. There is a resurgence of interest in the generation of monoclonal antibodies (mAbs) to the mycobacterial cell wall glycolipid lipoarabinomannan (LAM) to improve the limited sensitivity of currently available urinary LAM (U-LAM) detection tests for the diagnosis of TB (reviewed in Shah et al.3) For both diagnostic purposes and the investigation of protective efficacy, we are interested in exploring the breath and functions of human antibodies to Mtb, especially those to the Mtb surface. To better understand and study the spectrum of human antibodies targeting different AM epitopes at the monoclonal level, especially in individuals who can control
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