1887

Abstract

mAb CS-35 is representative of a large group of antibodies with similar binding specificities that were generated against the lipopolysaccharide, lipoarabinomannan (LAM), and which cross-reacted extensively with LAMs from and other mycobacteria. That this antibody also cross-reacts with the arabinogalactan (AG) of the mycobacterial cell wall, suggesting that it recognizes a common arabinofuranosyl (Ara)-containing sequence in AG and LAM, is demonstrated. The antibody reacted more avidly with ‘AraLAM’ (LAM with naked Ara termini) compared to ‘ManLAM’ (in which many Ara termini are capped with mannose residues) and mycolylarabinogalactan–peptidoglycan complex (in which the terminal Ara units are substituted with mycolic acids). Neither did the antibody bind to AG from knock-out mutants deficient in the branched hexa-Ara termini of AG. These results indicate that the terminal Ara residues of mycobacterial arabinan are essential for binding. Competitive ELISA using synthetic oligosaccharides showed that the branched hexa-Ara methyl glycoside [β-D-Ara-(1→2)-α-D-Ara-(1-)-(3 and 5)-α-D-Ara-(1→5)-α-D-Ara-OCH] was the best competitor among those tested. The related linear methyl glycoside, β-D-Ara-(1→2)-α-D-Ara-(1→5)-α-D-Ara-(1→5)-α-D-Ara-OCH, representing one linear segment of the branched hexa-Ara, was less effective and the other linear tetrasaccharide, β-D-Ara-(1→2)-α-D-Ara-(1→3)-α-D-Ara-(1→5)-α-D-Ara-OCH, was ineffective. The combined results suggest that the minimal epitope recognized by antibody CS-35 encompasses the β-D-Ara-(1→2)-α-D-Ara-(1→5)-α-D-Ara-(1→5)-α-D-Ara within the branched hexa-Ara motif of mycobacterial arabinans, whether present in LAM or AG.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-148-10-3049
2002-10-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/148/10/1483049a.html?itemId=/content/journal/micro/10.1099/00221287-148-10-3049&mimeType=html&fmt=ahah

References

  1. Belanger A. E, Besra G. S, Ford M. E, Mikusova K, Belisle J. T, Brennan P. J., Inamine J. M. 1996; The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc Natl Acad Sci USA 93:11919–11924
    [Google Scholar]
  2. Britton W. J, Hellqvist L, Basten A., Raison R. L. 1985; Mycobacterium leprae antigens involved in human immune responses. J Immunol 135:4171–4177
    [Google Scholar]
  3. Chatterjee D, Bozic C. M, McNeil M. R., Brennan P. J. 1991; Structural features of the arabinan component of the lipoarabinomannan of Mycobacterium tuberculosis . J Biol Chem 266:9652–9660
    [Google Scholar]
  4. Chatterjee D, Lowell K, Rivoire B, McNeil M. R., Brennan P. J. 1992a; Lipoarabinomannan of Mycobacterium tuberculosis . J Biol Chem 267:6234–6239
    [Google Scholar]
  5. Chatterjee D, Roberts A. D, Lowell K, Brennan P. J., Orme I. 1992b; Structural basis of lipoarabinomannan to induce secretion of tumor necrosis factor. Infect Immun 60:1249–1253
    [Google Scholar]
  6. Cisar J, Kabat E. A, Dorner M. M., Liao J. 1975; Binding properties of immunoglobin combining sites specific for terminal or nonterminal antigenic determinants in dextran. J Exp Med 142:435–459
    [Google Scholar]
  7. Cygler M, Rose D. R., Bundle D. R. 1991; Recognition of a cell surface oligosaccharide of pathogenic Salmonella by an antibody Fab fragment. Science 253:442–445
    [Google Scholar]
  8. Daffe M, Brennan P. J., McNeil M. R. 1990; Predominant structural features of the cell wall arabinogalactan of Mycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by1H and 13C NMR analyses. J Biol Chem 265:6734–6743
    [Google Scholar]
  9. Deng L, Mikusova K, Robuck K. G, Scherman M, Brennan P. J., McNeil M. R. 1995; Recognition of multiple effects of ethambutol on the metabolism of the mycobacterial cell envelope. Antimicrob Agents Chemother 39:694–701
    [Google Scholar]
  10. D’Souza F. W., Lowary T. L. 2000; The first total synthesis of a highly branched arabinofuranosyl hexasaccharide found at the nonreducing termini of mycobacterial arabinogalactan and lipoarabinomannan. Org Lett 2:1493–1495
    [Google Scholar]
  11. Escuyer V. E, Lety M.-A, Torelles J. B. 7 other authors 2001; The role of embA and embB gene products in the biosynthesis of terminal hexaarabinofuranosyl motif of Mycobacterium smegmatis arabinogalactan. J Biol Chem 276:48854–48862
    [Google Scholar]
  12. Frehel C., Leduc M. 1987; Cytochemical localization of lipopolysaccharides during peptidoglycan degradation of Escherichia coli cells. J Bacteriol 69:210–217
    [Google Scholar]
  13. Gaylord H, Brennan P. J, Young D. B., Buchanan T. M. 1987; Most Mycobacterium leprae carbohydrate reactive monoclonal antibodies are directed to lipoarabinomannan. Infect Immun 55:2860–2863
    [Google Scholar]
  14. Glaudemans C. P. J. 1987; Seven structurally different murine monoclonal galactan-specific antibodies show identity in their galactosyl-binding subsite arrangements. Mol Immunol 24:371–377
    [Google Scholar]
  15. Hamasur B, Kallenius G., Svenson S. B. 1999; Synthesis and immunologic characterization of Mycobacterium tuberculosis lipoarabinomannan specific oligosaccharide–protein conjugates. Vaccine 17:2853–2861
    [Google Scholar]
  16. Hirschfield G. R, McNeil M. R., Brennan P. J. 1990; Peptidoglycan-associated polypeptides of Mycobacterium tuberculosis . J Bacteriol 172:1005–1013
    [Google Scholar]
  17. Hunter S. W, Gaylord H., Brennan P. J. 1986; Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli. J Biol Chem 261:12345–12351
    [Google Scholar]
  18. Kaplan G, Gandhi R. R, Weinstein D. E, Levis W. R, Patarroyo M. E, Brennan P. J., Cohn Z. A. 1987; Mycobacterium leprae antigen-induced suppression of T-cell proliferation in vitro. J Immunol 138:3028–3034
    [Google Scholar]
  19. Khoo K.-H, Tang J.-B., Chatterjee D. 2001; Variation in mannose-capped terminal arabinan motifs of lipoarabinomannan from clinical isolates of Mycobacterium tuberculosis and Mycobacterium avium complex. J Biol Chem 276:3863–3871
    [Google Scholar]
  20. Kikuchi S, Ohinata A, Tsumuraya Y, Hashimoto Y, Kaneko Y., Matsushima H. 1993; Production and characterization of antibodies to the beta-(1→6)-galactotetraosyl group and their interaction with arabinogalactan-proteins. Planta 190:525–535
    [Google Scholar]
  21. Knox J. P, Linstead P. J, Peart J, Cooper C., Roberts K. 1991; Developmentally regulated epitopes of cell surface arabinogalactan proteins and their relation to root tissue pattern formation. Plant J 1:317–326
    [Google Scholar]
  22. Kotani S, Kato T, Matsuda T, Kato K., Misaki A. 1971; Chemical structure of the antigenic determinants of cell wall polysaccharide of Mycobacterium tuberculosis strain H37Rv. Biken J 14:379–387
    [Google Scholar]
  23. Levy S, York W. S, Stuike-Prill R, Meyer B., Staehelin L. A. 1991; Simulations of the static and dynamic molecular conformations of xyloglucan. The role of fucosylated side chain in surface specific side chain folding. Plant J 1:195–215
    [Google Scholar]
  24. McNeil M. R, Daffe M., Brennan P. J. 1991; Location of the mycolyl ester substituents in the cell walls of mycobacteria. J Biol Chem 266:13217–13223
    [Google Scholar]
  25. Means T. K, Wang S, Lien E, Yoshimura A, Golenbock D. T., Fenton M. J. 1999; Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis . J Immunol 163:3920–3927
    [Google Scholar]
  26. Mikusova K, Slayden R. A, Besra G. S., Brennan P. J. 1995; Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob Agents Chemother 39:2484–2489
    [Google Scholar]
  27. Misaki A, Seto N., Azuma I. 1974; Structure and immunological properties of D-arabino-D-galactans isolated from cell walls of Mycobacterium species. J Biochem 76:15–27
    [Google Scholar]
  28. Misaki A, Azuma I., Yamamura Y. 1977; Structural and immunochemical studies on D-arabino and D-mannan of Mycobacterium tuberculosis and other Mycobacterium species. J Biochem 82:1759–1770
    [Google Scholar]
  29. Molloy A, Gaudernack G, Lewis W. R, Cohn Z. A., Kaplan G. 1990; Suppression of T-cell proliferation by Mycobacterium and its products: the role of lipopolysaccharides. Proc Natl Acad Sci USA 87:973–977
    [Google Scholar]
  30. Moreno C, Mehlert A., Lamb J. 1988; The inhibitory effects of mycobacterial lipoarabinomannan and polysaccharides upon polyclonal and monoclonal human T cell proliferation. Clin Exp Immunol 74:206–210
    [Google Scholar]
  31. Oomen R. P, Young N. M., Bundle D. R. 1991; Molecular modeling of antibody–antigen complexes between the Brucella abortus O-chain polysaccharide and a specific monoclonal antibody. Protein Eng 4:427–433
    [Google Scholar]
  32. Pennell R. I, Janniche L, Scofield G. N, Booij H, de Vries S. C., Roberts K. 1992; Identification of a transitional cell state in the developmental pathway to carrot somatic embryogenesis. J Cell Biol 119:1371–1380
    [Google Scholar]
  33. Prinzis S, Chatterjee D., Brennan P. J. 1993; Structure and antigenicity of the phosphorylated lipoarabinomannan from Mycobacterium bovis BCG. J Gen Microbiol 139:2649–2658
    [Google Scholar]
  34. Schlesinger L. S, Hull S. R., Kaufman T. M. 1994; Binding of the terminal mannosyl units of lipoarabinomannan from a virulent strain of Mycobacterium tuberculosis to human macrophages. J Immunol 152:4070–4079
    [Google Scholar]
  35. Schlesinger L. S, Kaufman T. M, Iyer S, Hull S. R., Marchiando L. K. 1996; Differences in mannose receptor-mediated uptake of lipoarabinomannan from virulent and attenuated strains of Mycobacterium tuberculosis by human macrophages. J Immunol 157:4568–4575
    [Google Scholar]
  36. Sieling P. A, Chatterjee D, Porcelli S. A. 8 other authors 1995; CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269:227–230
    [Google Scholar]
  37. Takayama K., Kilburn J. O. 1989; Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis . Antimicrob Agents Chemother 33:1493–1499
    [Google Scholar]
  38. Telenti A, Philipp W. J, Sreevatsan S, Bernasconi C, Stockbauer K. E, Wieles B, Musser J. M., Jacobs W. R. Jr 1997; The emb operon, a unique gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med 3:567–570
    [Google Scholar]
  39. Tsuji S, Uehori J, Matsumoto M, Suzuki S. Y, Matsuhisa A, Toyoshima K., Seya T. 2001; Human intelectin is a novel soluble intelectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall. J Biol Chem 276:23456–23463
    [Google Scholar]
  40. Yin H, D’Souza F. W., Lowary T. L. 2002; Arabinofuranosides from mycobacteria: synthesis of a highly branched hexasaccharide and related fragments containing β-arabinofuranosyl residues. J Org Chem 67:892–903
    [Google Scholar]
  41. Yoshida A., Koide Y. 1997; Arabinofuranosyl-terminated and mannosylated lipoarabinomannans from Mycobacterium tuberculosis induce different levels of interleukin-12 expression in murine macrophages. Infect Immun 65:1953–1955
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-148-10-3049
Loading
/content/journal/micro/10.1099/00221287-148-10-3049
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error