Characterization of the antigenic heterogeneity of lipoarabinomannan, the major surface glycolipid of mycobacterium tuberculosis, and complexity of antibody specificities toward this antigen

Alok Choudhary, Deendayal Patel, William Honnen, Zhong Lai, Raja Sekhar Prattipati, Ruixiang Blake Zheng, Ying Chao Hsueh, Maria Laura Gennaro, Alfred Lardizabal, Blanca I. Restrepo, Moncerrato Garcia-Viveros, Maju Joe, Yu Bai, Ke Shen, Kamar Sahloul, John S. Spencer, Delphi Chatterjee, Tobias Broger, Todd L. Lowary, Abraham Pinter

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Lipoarabinomannan (LAM), the major antigenic glycolipid of Mycobacterium tuberculosis, is an important immunodiagnostic target for detecting tuberculosis (TB) infection in HIV-1–coinfected patients, and is believed to mediate a number of functions that promote infection and disease development. To probe the human humoral response against LAM during TB infection, several novel LAM-specific human mAbs were molecularly cloned from memory B cells isolated from infected patients and grown in vitro. The fine epitope specificities of these Abs, along with those of a panel of previously described murine and phage-derived LAM-specific mAbs, were mapped using binding assays against LAM Ags from several mycobacterial species and a panel of synthetic glycans and glycoconjugates that represented diverse carbohydrate structures present in LAM. Multiple reactivity patterns were seen that differed in their specificity for LAM from different species, as well as in their dependence on arabinofuranoside branching and nature of capping at the nonreducing termini. Competition studies with mAbs and soluble glycans further defined these epitope specificities and guided the design of highly sensitive immunodetection assays capable of detecting LAM in urine of TB patients, even in the absence of HIV-1 coinfection. These results highlighted the complexity of the antigenic structure of LAM and the diversity of the natural Ab response against this target. The information and novel reagents described in this study will allow further optimization of diagnostic assays for LAM and May facilitate the development of potential immunotherapeutic approaches to inhibit the functional activities of specific structural motifs in LAM. The Journal of Immunology, 2018, 200: 3053–3066.

Original languageEnglish (US)
Pages (from-to)3053-3066
Number of pages14
JournalJournal of Immunology
Volume200
Issue number9
DOIs
Publication statusPublished - May 1 2018

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this