Chapter 21 : Proteins and Antigens of

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Proteins and Antigens of , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818357/9781555819101_Chap21-1.gif /docserver/preview/fulltext/10.1128/9781555818357/9781555819101_Chap21-2.gif


The proteins of the causative agent of tuberculosis, , have been a major research topic almost since the days of the discovery of the organism by Robert Koch in 1882. The goals of subsequent efforts have been to identify antigens that may be important in conferring protection against tuberculosis. The search for improved diagnostic reagents such as improved skin test reagents and/or serological markers is another aspect of such studies. Obviously, each protein of , like proteins of any other organism, serves different functions. As discussed in this chapter, many bacterial proteins are highly conserved, not only within the genus but also in a broad range of other bacterial species. One example is the group of stress or heat shock proteins that are produced in abundant quantities by and that exhibit at least 50% homology at the amino acid level with stress proteins from other bacterial species. A new group of researchers were thereby recruited to the field from other disciplines, and the microorganism was soon approached at both the DNA level and the protein level by the development of monoclonal antibodies (MAbs) raised against . Five recombinant antigens have been produced in large enough quantities to be distributed to interested researchers through a WHO-organized "antigen bank". In gram-negative bacteria, the cell wall consists of three layers: the cytoplasmic membrane, the peptidoglycan layer, and an outer lipopolysaccharide-containing cell membrane.

Citation: Andersen Å, Brennan P. 1994. Proteins and Antigens of , p 307-332. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch21
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Example of CIE of BCG culture fluid (BCG c.fl.). The second-dimension gel contained rabbit anti-BCG immunoglobulins (anti-BCG), and the intermediate gel contained 100 μl of 0.1 M NaCl. Numbers refer to the CIE reference system introduced by Closs et al. (1980). Staining for the esterase activity was performed prior to Coomassie staining of the CIE plate. The figure was kindly provided by Morten Harboe, Oslo, Norway. ag, antigen.

Citation: Andersen Å, Brennan P. 1994. Proteins and Antigens of , p 307-332. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Example of SDS-PAGE of fractions of secreted proteins of Lane F contains the starting material: secreted proteins from devoid of autolytic products. Lanes 1 to 19 contain different fractions obtained after preparative SDS-PAGE and subsequent electroelution ( ). The figure was kindly provided by Peter Andersen, Copenhagen, Denmark.

Citation: Andersen Å, Brennan P. 1994. Proteins and Antigens of , p 307-332. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Kinetics of release of antigens into culture filtrates. Group 1 represents antigens rapidly secreted or excreted into the medium. Group 2 contains antigens secreted or released gradually throughout the culture period. Group 3 contains antigens present in SDS cell extracts that represent release of cytoplasmic constituents rather than secreted proteins. OD490, optical density at 490 nm.

Citation: Andersen Å, Brennan P. 1994. Proteins and Antigens of , p 307-332. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abou-Zeid, C.,, E. Filley,, J. Steele,, and G. A. W. Rook. 1987. A simple new method for using antigens separated by polyacrylamide gel electrophoresis to stimulate lymphocytes in vitro after converting bands cut from Western blots into antigen-bearing particles. J. Immunol. Methods 98:510.
2. Abou-Zeid, C.,, T. Garbe,, R. Lathigra,, H. Wiker,, M. Harboe,, G. A. W. Rook,, and D. B. Young. 1991. Genetic and immunological analysis of Mycobacterium tuberculosis fibronectin-binding proteins. Infect. Immun. 59:27122718.
3. Abou-Zeid, C.,, T. L. Ratliff,, H. G. Wiker,, M. Harboe,, J. Bennedsen,, and G. A. W. Rook. 1988a. Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG. Infect. Immun. 56:30463051.
4. Abou-Zeid, C.,, I. Smith,, J. M. Grange,, T. L. Ratliff,, J. Steele,, and G. A. W. Rook. 1988b. The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies. J. Gen. Microbiol. 134:531538.
5. Andersen, Å. B. Unpublished data.
6. Andersen, Å. B.,, P. Andersen,, and L. Ljungqvist. 1992a. Structure and function of a 40,000-molecular-weight protein antigen of Mycobacterium tuberculosis. Infect. Immun. 60:23172323.
7. Andersen, Å. B.,, and E. B. Hansen. 1989. Structure and mapping of antigenic domains of protein antigen b, a 38,000-molecular-weight protein of Mycobacterium tuberculosis. Infect. Immun. 57:24812488.
8. Andersen, Å. B.,, and E. B. Hansen. 1993. Cloning of the lysA gene from Mycobacterium tuberculosis. Gene 124:105109.
9. Andersen, Å. B.,, L. Ljungqvist,, K. HaslØv,, and M. W. Bentzon. 1991a. MPB64 possesses 'tuberculosis-complex'-specific B- and T-cell epitopes. Scand. J. Immunol. 34:365372.
10. Andersen, Å. B.,, L. Ljungqvist,, and M. Olsen. 1990. Evidence that protein antigen b of Mycobacterium tuberculosis is involved in phosphate metabolism. J. Gen. Microbiol. 136:477480.
11. Andersen, Å. B.,, A. Worsaae,, and S. D. Chaparas. 1988a. Isolation and characterization of recombinant lambda gt11 bacteriophages expressing eight different mycobacterial antigens of potential immunological relevance. Infect. Immun. 56:13441351.
12. Andersen, Å. B.,, Z. L. Yuan,, K. HaslØv,, B. Vergmann,, and J. Bennedsen. 1986. Interspecies reactivity of five monoclonal antibodies to Mycobacterium tuberculosis as examined by immunoblotting and enzyme-linked immunosorbent assay. J. Clin. Microbiol. 23:446451.
13. Andersen, P.,, D. Askgaard,, A. Gottshau,, J. Bennedsen,, S. Nagai,, and I. Heron. 1992b. Identification of immunodominant antigens during infection with Mycobacterium tuberculosis. Scand. J. Immunol. 36: 823831.
14. Andersen, P.,, D. Askgaard,, L. Ljungqvist,, J. Bennedsen,, and I. Heron. 1991b. Proteins released from Mycobacterium tuberculosis during growth. Infect. Immun. 59:19051910.
15. Andersen, P.,, D. Askgaard,, L. Ljungqvist,, M. W. Bentzon,, and I. Heron. 1991c. T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis. Infect. Immun. 59:15581563.
16. Andersen, P.,, and I. Heron. 1993a. Specificity of a protective memory immune response against Mycobacterium tuberculosis. Infect. Immun. 61:844851.
17. Andersen, P.,, and I. Heron. 1993b. Simultaneous electroelution of whole SDS-polyacrylamide gels for the direct cellular analysis of complex protein mixtures. J. Immunol. Methods 161:2939.
18. Anderson, D. C.,, M. E. Barry,, and T. M. Buchanan. 1988b. Exact definition of species-specific and cross-reactive epitopes of the 65-kilodalton protein of Mycobacterium leprae using synthetic peptides. J. Immunol. 141:607613.
19. Ang, D.,, K. Liberek,, D. Skowyra,, M. Zylicz,, and C. Georgeopolous. 1991. Biological role and regulation of the universally conserved heat shock proteins. J. Biol. Chem. 266:2423324236.
20. Bachmann, B. J. 1990. Linkage map of Escherichia coli K-12, edition 8. Microbiol. Rev. 54:130197.
21. Baess, I.,, and B. Mansa. 1978. Determination of genome size and base ratio on deoxyribonucleic acid from mycobacteria. Acta Pathol. Microbiol. Scand. Sect. B 86:309312.
22. Baird, P. N.,, L. M. C. Hall,, and A. R. M. Coates. 1989. Cloning and sequence analysis of the 10 kDa antigen gene of Mycobacterium tuberculosis. J. Gen. Microbiol. 135:931939.
23. Barnes, P. F.,, V. Mehra,, G. R. Hirchfield,, S. J. Fong,, C. Abou-Zeid,, G. Rook,, G. A. W. Hunter,, P. J. Brennan,, and R. Modlin. 1989. Characterization of T cell antigens associated with the cell wall protein-peptidoglycan complex of Mycobacterium tuberculosis. J. Immunol. 143:2656.
24. Barnes, P. F.,, V. Mehra,, B. Rivoire,, S.-J. Fong,, P. J. Brennan,, M. S. Voegtline,, P. Minden,, R. A. Houghten,, B. R. Bloom,, and R. L. Modlin. 1992. Immuno-reactivity of a 10-kDa antigen of Mycobacterium tuberculosis. J. Immunol. 148:18351840.
25. Borremans, M.,, L. De Wit,, G. Volkaert,, J. Ooms,, J. De Bruyn,, K. Huygen,, J. P. Van Vooren,, M. Stelandre,, R. Verhofstadt,, and J. Content. 1989. Cloning, sequence determination, and expression of a 32 kilodalton-protein gene of Mycobacterium tuberculosis. Infect. Immun. 57:31233130.
26. Buchmeier, N. A.,, and F. Heffron. 1990. Induction of Salmonella stress proteins upon infection of macrophages. Science 248:730732.
27. Bulletin of the World Health Organization. 1983. Memorandum from a WHO meeting: plan of action for research in the immunology of tuberculosis. Bull. W.H.O. 61:779785.
28. Carlin, N. I. A.,, S. Lofdahl,, and M. Magnusson. 1992. Monoclonal antibodies specific for elongation factor Tu and complete nucleotide sequence of the tuf gene in Mycobacterium tuberculosis. Infect. Immun. 60: 31363142.
29. Chamberlain, N. R.,, M. E. Brandt,, A. L. Erwin,, J. D. Radolf,, and M. V. Norgard. 1989. Major integral membrane protein immunogens of Treponema pallidum are proteolipids. Infect. Immun. 57:28722877.
30. Closs, O.,, M. Harboe,, N. H. Axelsen,, K. Bunch-Christensen,, and M. Magnusson. 1980. The antigens of Mycobacterium bovis, strain BCG, studied by crossed immunoelectrophoresis: a reference system. Scand. J. Immunol. 12:249263.
31. Coates, A. R. M.,, J. Hewitt,, B. W. Allen,, J. Ivanyi,, and D. A. Mitchison. 1981. Antigenic diversity of Mycobacterium tuberculosis and Mycobacterium bovis detected by means of monoclonal antibodies. Lancet ii:167169.
32. Cohen, I. R.,, and D. B. Young. 1991. Autoimmunity, microbial immunity and the immunological homonculus. Immunol. Today 12:105110. Cole, S. Personal communication.
33. Content, J.,, A. de la Cuvellerie,, L. de Wit,, V. Vincent-Levy-Frebault,, J. Ooms,, and J. de Bruyn. 1991. The genes coding for the antigen 85 complexes of Mycobacterium tuberculosis and Mycobacterium bovis BCG are members of a gene family: cloning, sequence determination, and genomic organization of the gene coding for antigen 85-C of M. tuberculosis. Infect. Immun. 59:32053212.
34. Daniel, T. M.,, and B. W. Janicki. 1978. Mycobacterial antigens: a review of their isolation, chemistry, and immunological properties. Microbiol. Rev. 42:84113.
35. Daugelat, S.,, H. Guile,, B. Schoel,, and S. H. E. Kaufman. 1992. Secreted antigens of Mycobacterium tuberculosis: characterization with T lymphocytes from patients and contacts after two-dimensional separation. J. Infect. Dis. 166:186190.
36. De Bruyn, J.,, R. Bosnians,, J. Nyabenda,, and J. P. Van Vooren. 1989. Effect of zinc deficiency on the appearance of two immunodominant protein antigens (32kDa and 65kDa) in culture filtrates of mycobacteria. J. Gen. Microbiol. 135:7984.
37. De Bruyn, J.,, J. Huygen,, R. Bosnians,, M. Fauville,, R. Lippens,, J. P. Van Vooren,, P. Falmagne,, M. Weckx,, H. G. Wiker,, M. Harboe,, and M. Turneer. 1987. Purification, characterization and identification of a 32 kDa protein antigen of Mycobacterium bovis BCG. Microb. Pathog. 2:351366.
38. Delforge, D.,, E. Depiereux,, X. de Bolle,, E. Feytmans,, and J. Remade. 1993. Similarities between alanine dehydrogenase and the N-terminal part of pyridine nucleotide transhydrogenase and their possible implication in the virulence mechanism of Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 190:10731079.
39. Deres, K.,, H. Schild,, K. H. Wiesmuller,, G. Jung,, and H. G. Ramensee. 1989. In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature (London) 342:561564.
40. De Wit, L.,, A. de la Cuvellerie,, J. Ooms,, and J. Content. 1990. Nucleotide sequence of the 32 kDa-protein gene (antigen 85A) of Mycobacterium bovis BCG. Nucleic Acids Res. 18:3995.
41. De Wit, T. F. R.,, S. Bekelie,, A. Osland,, T. L. Miko,, P. W. M. Hermans,, D. van Soolingen,, J.-W. Drijfhout,, R. Schoningh,, A. A. M. Janson,, and J. E. R. Thole. 1992. Mycobacteria contain two groEL genes: the second Mycobacterium leprae groEL gene is arranged in an operon with groES. Mol. Microbiol. 6:19952007.
42. Engers, H. D., and Workshop Participants. 1985. Results of a World Health Organization-sponsored workshop on monoclonal antibodies to Mycobacterium leprae. Infect. Immun. 48:603605. (Letter to the editor.)
43. Engers, H. D., and Workshop Participants. 1986. Results of a World Health Organization-sponsored workshop to characterize antigens recognized by mycobacterium-specific monoclonal antibodies. Infect. Immun. 51:718720. (Letter to the editor.)
44. Espitia, C.,, M. Elinos,, R. Hernandez-Pando,, and R. Mancilla. 1992. Phosphate starvation enhances expression of the immunodominant 38-kilodalton protein antigen of Mycobacterium tuberculosis: demonstration by immunogold electron microscopy. Infect. Immun. 60:29983001.
45. Fridovic, I. 1978. The biology of oxygen radicals. Science 201:875880.
46. Furano, A. V. 1978. Direct demonstration of duplicate tuf genes in enteric bacteria. Proc. Natl. Acad. Sci. USA 75:31043108.
47. Garbe, T.,, D. Harris,, M. Vordermeier,, R. Lathigra,, J. Ivanyi,, and D. Young. 1993. Expression of the Mycobacterium tuberculosis 19-kiIodalton antigen in Mycobacterium smegmatis: immunological analysis and evidence of glycosylation. Infect. Immun. 61:260267.
48. Garbe, T.,, C. Jones,, I. Charles,, G. Dougan,, and D. Young. 1990. Cloning and characterization of the aroA gene from Mycobacterium tuberculosis. J. Bacteriol. 172:67746782.
49. Garsia, R. J.,, L. Hellqvist,, R. J. Booth,, A. J. Radford,, W. J. Britton,, L. Astbury,, R. J. Trent,, and A. Basten. 1989. Homology of the 70-kilodalton antigens from Mycobacterium leprae and Mycobacterium bovis with the Mycobacterium tuberculosis 71-kilodalton antigen and with the conserved heat shock protein 70 of eucaryotes. Infect. Immun. 57:204212.
50. Godfrey, H. P.,, Z. Feng,, S. Mandy,, K. Mandy,, K. Huygen,, J. De Bruyn,, C. Abou-Zeid,, H. G. Wiker,, S. Nagai,, and H. Tasaka. 1992. Modulation of expression of delayed hypersensitivity by mycobacterial antigen 85 fibronectin-binding proteins. Infect. Immun. 60:25222528.
51. Guld, J.,, W. W. Bentzon,, M. A. Bleiker,, W. A. Griep,, M. Magnusson,, and H. Waaler. 1958. Standardization of a new batch of purified tuberculin (PPD) intended for international use. Bull. Org. Mond. Sante 19:845951.
52. Guile, H.,, B. Schoel,, and S. H. Kaufmann. 1990. Direct blotting with viable cells of protein mixtures separated by two-dimensional gel electrophoresis. J. Immunol. Methods 133:253261.
53. Harboe, M.,, and S. Nagai. 1984. MPB70, a unique antigen of Mycobacterium bovis BCG1-3. Am. Rev. Respir. Dis. 129:444452.
54. Harboe, M.,, S. Nagai,, M. E. Patarroyo,, M. L. Torres,, C. Ramirez,, and N. Cruz. 1986. Properties of proteins MPB64, MPB70, and MPB80 of Mycobacterium bovis BCG. Infect. Immun. 52:293302.
55. Harboe, M.,, and A. J. Quayle. 1991. Heat shock proteins: friend and foe? Clin. Exp. Immunol. 86: 25.
56. Harboe, M.,, and H. G. Wiker. 1992. The 38-kDa protein of Mycobacterium tuberculosis: a review. J. Infect. Dis. 166:874884.
57. HaslØv, K.,, Å. B. Andersen,, L. Ljungqvist,, and M. W. Bentzon. 1990. Comparison of the immunological activity of five defined antigens from Mycobacterium tuberculosis in seven inbred guinea pig strains. The 38-kDa antigen is immunodominant. Scand. J. Immunol. 31:503514.
58. Hoiseth, S. K.,, and B. A. D. Stocker. 1981. Aromatic-dependent Salmonella typhimurium are nonvirulent and effective as live vaccines. Nature (London) 291:238239.
59. Honoré N.,, S. Bergh,, S. Chanteau,, F. Doucet-Populaire,, K. Eiglmeier,, T. Gamier,, C. Georges,, P. Launois,, T. Limpaiboon,, S. Newton,, K. Niang,, P. del Portillo,, G. R. Ramesh,, P. Reddi,, P. R. Ridel,, N. Sittisombut,, S. Wu-Hunter,, and S. T. Cole. 1993. Nucleotide sequence of the first cosmid from the Mycobacterium leprae genome project: structure and function of the Rif-Str regions. Mol. Microbiol. 7:207214.
60. Hubbard, R. D.,, C. M. Flory,, and F. M. Collins. 1992. Immunization of mice with mycobacterial culture filtrate proteins. Clin. Exp. Immunol. 87:9498.
61. Husson, R. N.,, and R. A. Young. 1987. Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agent of tuberculosis and leprosy share an immunodominant antigen. Proc. Natl. Acad. Sci. USA 84:16791683.
62. Huygen, K.,, K. Palfliet,, F. Jurion,, J. Hilgers,, R. ten Berg,, J.-P. van Vooren,, and J. de Bruyn. 1988a. 7Z-2-linked control of in vitro gamma interferon production in response to a 32-kilodalton antigen (P32) of Mycobacterium bovis bacillus Calmette-Guerin. Infect. Immun. 56:31963200.
63. Huygen, K.,, J.-P. van Vooren,, M. Turneer,, R. Bos-mans,, P. Dierckx,, and J. de Bruyn. 1988b. Specific lymphoproliferation, gamma interferon production, and serum immunoglobulin G directed against a purified 32 kDa mycobacterial protein antigen (P32) in patients with active tuberculosis. Scand. J. Immunol. 27:187194.
64. Kadival, G. V.,, S. D. Chaparas,, and D. Hussong. 1987. Characterization of serologic and cell-mediated reactivity of a 38-kDa antigen isolated from Mycobacterium tuberculosis. J. Immunol. 139:24472451.
65. Kale, Ab B.,, R. Kiessling,, J. D. A. van Embden,, J. E. R. Thole,, D. S. Kumararatne,, P. Pisa,, A. Wondimu,, and T. H. M. Ottenhoff. 1990. Induction of antigen-specific CD4+ HLA-DR-restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65-kDa heat-shock protein. Eur. J. Immunol. 20:369377.
66. Kawamura, I.,, H. Tsukada,, H. Yoshikawa,, M. Fujita,, K. Nomoto,, and M. Mitsuyama. 1992. IFN-γ-producing ability as a possible marker for the protective T cells against Mycobacterium bovis BCG in mice. J. Immunol. 148:28872893.
67. Khanolkar-Young, S.,, A. H. J. Kolk,, B. Andersen,, J. Bennedsen,, P. J. Brennan,, B. Rivoire,, S. Kuijper,, K. P. W. J. McAdam,, C. Abe,, H. V. Batra,, S. D. Chaparas,, G. Damiani,, M. Singh,, and H. D. Engers. 1992. Results of the Third Immunology of Leprosy/ Immunology of Tuberculosis Antimycobacterial Monoclonal Antibody Workshop. Infect. Immun. 60:39253927.
68. Klausen, J. Unpublished data.
69. Koch, R. 1882. Die Atiologie der Tuberkulose. Berliner Klin. Wochenschr. 15:221230.
70. Koch, R. 1891. Weitere Mitteilung iiber das Tuberkulin. Dtsch. Med. Wochenschr. 43:11891192.
71. Koch, R. 1897. Uber neue Tuberkulinpraparate. Dtsch. Med. Wochenschr. 14:209213.
72. Kong, T. H.,, A. R. M. Coates,, P. D. Butcher,, C. J. Hickman,, and T. M. Shinnick. 1993. Mycobacterium tuberculosis expresses two chaperonin-60 homologs. Proc. Natl. Acad. Sci. USA 90:26082612.
73. Lamb, J. R.,, J. Ivanyi,, A. D. M. Rees,, J. B. Rothbard,, K. Howland,, R. A. Young,, and D. B. Young. 1987. Mapping of T cell epitopes using recombinant antigens and synthetic peptides. EMBO J. 6:12451249.
74. Landi, S., 1984. Production and standardization of tuberculin, p. 505535. In G. P. Kubica, and L. G. Wayne (ed.), The Mycobacteria—a Sourcebook, part A. Marcel Dekker, Inc., New York.
75. Lathigra, R.,, W. Alexander,, K. Stover,, J. Coadwell,, R. Young,, and D. Young. J. Biol. Chem., in press.
76. Lathigra, R. B.,, D. B. Young,, D. Sweetser,, and R. A. Young. 1988. A gene from Mycobacterium tuberculosis which is homologous to the DnaJ heat shock protein of E. coli. Nucleic Acids Res. 16:1636.
77. Lee, B.-Y.,, S. A. Hefta,, and P. J. Brennan. 1992. Characterization of the major membrane protein of virulent Mycobacterium tuberculosis. Infect. Immun. 60:20662074.
78. Li, H.,, J. C. Ulstrup,, T. 0. Jonassen, K. Melby, S. Nagai, and M. Harboe. 1993. Evidence for absence of the MPB64 gene in some substrains of Mycobacterium bovis BCG. Infect. Immun. 61:17301734.
79. Ljungqvisl, L.,, A. Worsaae,, and I. Heron. 1988. Antibody responses against Mycobacterium tuberculosis in 11 strains of inbred mice: novel monoclonal antibody specificities generated by fusions, using spleens from BALB.B10 and CBA/J mice. Infect. Immun. 56:19941998.
80. Luecke, H.,, and F. A. Quiocho. 1990. High specificity of a phosphate transport protein determined by hydrogen bonds. Nature (London) 347:402406.
81. Lyon, R. H.,, H. H. Wendell,, and C. Costas-Martinez. 1970. Utilization of amino acids during growth of Mycobacterium tuberculosis in rotary cultures. Infect. Immun. 1:513520.
82. Magnusson, M., 1967. Das Tuberkulin. Herstellung, Reinigung, Standardiserung und chemischer Aufbau, p. 191237. In G. Meissner, and A. Schmiedel (ed.), Mykobakterien und Mykobakterielle Krankheiten, teil II. VEB Gustav Fischer Verlag Jena, Munich..
83. Magnusson, M.,, and M. W. Bentzon. 1958. Preparation of purified tuberculin RT 23. Bull. Org. Mond. Sante 19:829843.
84. Matsuo, K.,, R. Yamaguchi,, A. Yamazaki,, H. Tasaka,, K. Teresaka,, and T. Yamada. 1990. Cloning and expression of the gene for the cross-reactive a antigen of Mycobacterium kansasii. Infect. Immun. 58:550556.
85. Matsuo, K.,, R. Yamaguchi,, A. Yamazaki,, H. Tasaka,, and T. Yamada. 1988. Cloning and expression of the Mycobacterium bovis BCG gene for extracellular a antigen. J. Bacteriol. 170:38473854.
86. Mehra, V.,, B. R. Bloom,, A. C. Bajardi,, C. L. Grisso,, P. A. Sieling,, D. Alland,, J. Convit,, X. Fan,, S. W. Hunter,, P. J. Brennan,, T. H. Rea,, and R. L. Modlin. 1992. A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein. J.Exp. Med. 175:275284.
87. Mehra, V.,, D. Sweetser,, and R. A. Young. 1986. Efficient mapping of protein antigenic determinants. Proc. Natl. Acad. Sci. USA 83:70137017.
88. Munk, M. E.,, T. M. Shinnick,, and S. H. E. Kaufmann. 1990. Epitopes of the mycobacterial heat shock protein 65 for human T cells comprise different structures. Immunobiology 180:272277.
89. Murray, P. J.,, and R. A. Young. 1992. Stress and immunological recognition in host-pathogen interactions. J. Bacteriol. 174:41934196.
90. Mustafa, A. S.,, F. Oftung,, A. Deggerdal,, H. K. Gill,, R. A. Young,, and T. Godal. 1988. Gene isolation with human T lymphocyte probes. Isolation of a gene that expresses an epitope recognized by T cells specific for Mycobacterium bovis BCG and pathogenic mycobacteria. J. Immunol. 141:27292733.
91. Nagai, S.,, H. G. Wiker,, M. Harboe,, and M. Kinomoto. 1991. Isolation and partial characterization of major protein antigens in the culture fluid of Mycobacterium tuberculosis. Infect. Immun. 59:372382.
92. Neidhardt, F. .,, and R. A. VanBogelen,. 1987. Heat shock response, p. 13341345. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, vol. 2. American Society for Microbiology, Washington, D.C..
93. Nielsen, J. B. K.,, and J. O. Lampen. 1982. Glyceridecysteine lipoproteins and secretion by gram-positive bacteria. J. Bacteriol. 152:315322.
94. Oettinger, T.,, and Å. B. Andersen. Unpublished data.
95. Oliver, D. 1985. Protein secretion in Escherichia coli. Annu. Rev. Microbiol. 39:615648.
96. Orme, I. M. 1988a. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection. J. Immunol. 140:35893593.
97. Orme, I. M. 1988b. Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance, in mice inoculated with killed mycobacterial vaccines. Infect. Immun. 56:33103312.
98. Orme, I. M.,, P. Andersen,, and W. H. Boom. 1993. The T cell response to Mycobacterium tuberculosis. J. Infect. Dis. 167:14811497.
99. Orme, I. M.,, E. S. Miller,, A. D. Roberts,, S. K. Furney,, J. P. Griffin,, K. M. Dobos,, D. Chi,, B. Rivoire,, and P. J. Brennan. 1992. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. J. Immunol. 148:189196.
100. Pal, P. G.,, and M. A. Horwitz. 1992. Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis. Infect. Immun. 60:47814792.
101. Peake, P.,, A. Basten,, and W. J. Britton. 1991. Characterization and functional properties of the 70-kDa protein of Mycobacterium bovis. J. Biol. Chem. 266:2082820832.
102. Polla, B. S. 1988. A role for heat shock proteins in inflammation? Immunol. Today 9:134137.
103. Pugsley, A. P.,, D. d'Enfert,, I. Reyss,, and M. G. Kornacker. 1990. Genetics of extracellular protein secretion by gram-negative bacteria. Annu. Rev. Genet. 24:6790.
104. Rambukkana, A.,, P. K. Das,, A. Chand,, J. G. Baas,, D. G. Groothuis,, and A. H. J. Kolk. 1991. Subcellular distribution of monoclonal antibody defined epitopes on immunodominant Mycobacterium tuberculosis proteins in the 30-kDa region: identification and localization of 29/33-kDa doublet proteins on mycobacterial cell wall. Scand. J. Immunol. 33:763775.
105. Ratlinff T. L.,, J. O. Palmer,, J. McGarr,, and E. J. Brown. 1987. Intravesical bacillus Calmette-Guenn therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of bacillus Calmette-Guérin. Cancer Res. 47:17621766.
106. Reitzer, L. J.,, and B. Magasanik,. 1987. Ammonia assimilation and the biosynthesis of glutamine, glutamate, aspartate, asparagine, L-alanine, and D-alanine, p. 302320. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C..
107. Ridell, M.,, R. öhman,, and G. Wallerström. 1987. Characterization of mycobacterial immunoprecipitates by selective staining of enzymes. J. Gen. Microbiol. 133:19831986.
108. Romain, F.,, J. Augier,, P. Pescher,, and G. Marchal. 1993a. Isolation of a proline-rich mycobacterial protein eliciting delayed-type hypersensitivity reactions only in guinea pigs immunized with living mycobacteria. Proc. Natl. Acad. Sci. USA 90:53225326.
109. Romain, F.,, A. Laqueyrerie,, P. Militzer,, P. Pescher,, P. Chavarot,, M. Lagranderie,, G. Auregan,, M. Gheorghiu,, and G. Marchal. 1993b. Identification of a Mycobacterium bovis BCG 45/47-kilodalton antigen complex, an immunodominant target for antibody response after immunization with living bacteria. Infect. Immun. 61:742750.
110. Rook, G. A. W.,, J. Steele,, S. Barnass,, J. Mace,, and J. L. Stanford. 1986. Responsiveness to live M. tuberculosis, and common antigens, of sonicate-stimulated T cell lines from normal donors. Clin. Exp. Immunol. 63:105110.
111. Seibert, F. B.,, and J. T. Glenn. 1941. Tuberculin purified protein derivative. Preparation and analyses of a large quantity for standard. Am. Rev. Tuberc. 44:925.
112. Seibert, F. B.,, and B. Munday. 1932. The chemical compositions of the active principles of tuberculin. XV. A precipitated purified tuberculin protein suitable for the preparation of a standard tuberculin. Am. Rev. Tuberc. 25:724737.
113. Shinnick, T. M. 1987. The 65-kilodalton antigen of Mycobacterium tuberculosis. J. Bacteriol. 169: 10801088.
114. Shinnick, T. M.,, C. Krat,, and S. Schadow. 1987a. Isolation and restriction site maps of the genes encoding five Mycobacterium tuberculosis proteins. Infect. Immun. 55:17181721.
115. Shinnick, T. M.,, D. Sweetser,, J. Thole,, J. van Embden,, and R. A. Young. 1987b. The etiologic agents of leprosy and tuberculosis share an immunoreactive protein antigen with the vaccine strain Mycobacterium bovis BCG. Infect. Immun. 55:19321935.
116. Thole, J. E. R.,, H. G. Dauwerse,, P. K. Das,, D. G. Groothuis,, L. M. Schouls,, and J. D. A. van Embden. 1985. Cloning of Mycobacterium bovis BCG DNA and expression of antigens in Escherichia coli. Infeet. Immun. 50:800806.
117. Thole, J. E. R.,, W. J. Keulen,, A. H. J. Kolk,, D. G. Groothuis,, L. G. Berwald,, R. H. Tiesjema,, and J. D. A. van Embden. 1987. Characterization, sequence determination, and immunogenicity of a 64-kilodalton protein of Mycobacterium bovis BCG expressed in Escherichia coli K-12. Infect. Immun. 55:14661475.
118. Thole, J. E. R.,, R. Schdningh,, A. A. M. Janson,, T. Garbe,, Y. E. Cornelisse,, J. E. Clark-Curtiss,, A. H. J. Kolk,, T. H. M. Ottenhoff,, R. R. P. De Vries,, and C. Abou-Zeid. 1992. Molecular and immunological analysis of a fibronectin-binding protein antigen secreted by Mycobacterium leprae. Mol. Microbiol. 6:153163.
119. Thole, J. E. R.,, and R. van der Zee,. 1990. The 65kD antigen: molecular studies on a ubiquitous antigen, p. 3767. In J. McFadden (ed.), Molecular Biology of the Mycobacteria. Academic Press Ltd., London.
120. Torriani, A. 1990. From cell membrane to nucleotides: the phosphate regulon in Escherichia coli.Bioessays 12:371376.
121. Torriani-Gorini, A.,, F. G. Rothman,, S. Silver,, A. Wright,, and E. Yagil (ed.). 1987. Phosphate Metabolism and Cellular Regulation in Microorganisms. American Society for Microbiology, Washington, D.C..
122. Trias, J.,, V. Jarlier,, and R. Benz. 1992. Porins in the cell wall of mycobacteria. Science 258:14791481.
123. Van de Klundert, J. A. M.,, P. Van der Meide,, P. Van de Putte,, and L. Bosch. 1978. Mutants of Escherichia coli altered in both genes coding for the elongation factor Tu. Proc. Natl. Acad. Sci. USA 75:44704473.
124. Vordermeier, H. M.,, D. P. Harris,, G. Friscia,, E. Roman,, H. M. Surcel,, C. Moreno,, G. Pasvol,, and J. Ivanyi. 1992a. T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope of the 38-kDa antigen in patients with active disease. Eur. J. Immunol. 22:26312637.
125. Vordermeier, H. M.,, D. P. Harris,, P. K. Mehrotra,, E. Roman,, A. Elsaghier,, C. Moreno,, and J. Ivanyi. 1992b. M. tuberculosis-complex specific T-cell stimulation and DTH reactions induced with a peptide from the 38-kDa protein. Scand. J. Immunol. 35: 711718.
126. Vordermeier, H. M.,, D. P. Harris,, E. Roman,, R. Lathigra,, C. Moreno,, and J. Ivanyi. 1991. Identification of T-cell stimulatory peptides from the 38-kDa protein of Mycobacterium tuberculosis. J. Immunol. 147:10231029.
127. Wallis, R. S.,, M. Amir-Tahmasseb,, and J. J. Ellner. 1990. Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte Western blot. Proc. Natl. Acad. Sci. USA 87:33483352.
128. Wallis, R. S.,, H. Fujiwara,, and J. J. Ellner. 1986. Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens. J. Immunol. 136:193196.
129. Wallis, R. S.,, R. Paranjape,, and M. Phillips. 1993. Identification by two-dimensional gel electrophoresis of a 58-kilodalton tumor necrosis factor-inducing protein of Mycobacterium tuberculosis. Infect. Immun. 61:627632.
130. Wiker, H. G.,, and M. Harboe. 1992. The antigen 85 complex: a major secretion product of Mycobacterium tuberculosis. Microbiol. Rev. 56:648661.
131. Wiker, H. G.,, M. Harboe,, J. Bennedsen,, and O. Closs. 1988. The antigens of Mycobacterium tuberculosis, H37Rv, studied by crossed Immunoelectrophoresis. Comparison with a reference system for Mycobacterium bovis, BCG. Scand. J. Immunol. 27:223239.
132. Wiker, H. G.,, M. Harboe,, and T. E. Lea. 1986a. Purification and characterization of two protein antigens from the heterogenous BCG85 complex in Mycobacterium bovis BCG. Int. Arch. Allergy Appl. Immun. 81:298306.
133. Wiker, H. G.,, M. Harboe,, and S. Nagai. 1991. A localization index for distinction between extracellular and intracellular antigens of Mycobacterium tuberculosis. J. Gen. Microbiol. 137:875884.
134. Wiker, H. G.,, M. Harboe,, S. Nagai,, M. E. Patarroyo,, C. Ramirez,, and N. Cruz. 1986b. MPB59, a widely cross-reacting protein of Mycobacterium bovis BCG. Int. Arch. Allergy Appl. Immun. 81:307314.
135. Wiker, H. G.,, K. Sletten,, S. Nagai,, and M. Harboe. 1990. Evidence for three separate genes encoding the proteins of the mycobacterial antigen 85 complex. Infect. Immun. 58:272274.
136. Worsaae, A.,, L. Ljungqvist,, K. Haslov,, I. Heron,, and J. Bennedsen. 1987. Allergenic and blastogenic reactivity of three antigens from Mycobacterium tuberculosis in sensitized guinea pigs. Infect. Immun. 55:29222927.
137. Worsaae, A.,, L. Ljungqvist,, and I. Heron. 1988. Monoclonal antibodies produced in BALB.B10 mice define new antigenic determinants in culture filtrate preparations of Mycobacterium tuberculosis. J. Clin. Microbiol. 26:26082614.
138. Wright, G. L.,, and D. B. Roberts. 1974. Two-dimensional Immunoelectrophoresis of mycobacterial antigens. Comparison with a reference system. Am. Rev. Respir. Dis. 109:306310.
139. Yamaguchi, R.,, K. Matsuo,, A. Yamazaki,, C. Abe,, S. Nagai,, K. Terasaka,, and T. Yamada. 1989. Cloning and characterization of the gene for immunogenic protein MPB64 of Mycobacterium bovis BCG. Infect. Immun. 57:283288.
140. Young, D.,, L. Kent,, A. Rees,, J. Lamb,, and J. Ivanyi. 1986. Immunological activity of a 38-kilodalton protein purified from Mycobacterium tuberculosis. Infect. Immun. 54:177183.
141. Young, D.,, R. Lathigra,, R. Hendrix,, D. Sweetser,, and R. A. Young. 1988. Stress proteins are immune targets in leprosy and tuberculosis. Proc. Natl. Acad. Sci. USA 85:42674270.
142. Young, D.,, E. Roman,, C. Moreno,, R. O'Brien,, and W. Born. 1993. Molecular chaperones and the immune response. Phil. Trans. R. Soc. London Ser. B 339: 363368.
143. Young, D. B.,, and T. R. Garbe. 1991a. Heat shock proteins and antigens of Mycobacterium tuberculosis. Infect. Immun. 59:30863093.
144. Young, D. B.,, and T. R. Garbe. 1991b. Lipoprotein antigens of Mycobacterium tuberculosis. Res. Microbiol. 142:5565.
145. Young, D. B.,, S. H. E. Kaufmann,, P. W. M. Hermans,, and J. E. R. Thole. 1992. Mycobacterial protein antigens: a compilation. Mol. Microbiol. 6:133145.
146. Young, D. B.,, and J. R. Lamb. 1986. T lymphocytes respond to solid-phase antigen: a novel approach to the molecular analysis of cellular immunity. Immunology 59:167171.
147. Young, R. A.,, B. R. Bloom,, C. M. Grossinsky,, J. Ivany,, D. Thomas,, and R. W. Davis. 1985a. Dissection of Mycobacterium tuberculosis antigens using recombinant DNA. Proc. Natl. Acad. Sci. USA 82:25832587.
148. Young, R. A.,, V. Mehra,, D. Sweetser,, T. Buchanan,, J. Clark-Curtiss,, R. W. Davis,, and B. R. Bloom. 1985b. Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae. Nature (London) 316:450452.
149. Zhang, Y.,, B. Heym,, B. Allen,, D. Young,, and S. Cole. 1992. The catalase-peroxidase gene and isoniazide resistance of Mycobacterium tuberculosis. Nature (London) 358:591593.
150. Zhang, Y.,, R. Lathigra,, T. Garbe,, D. Catty,, and D. Young. 1991. Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis. Mol. Microbiol. 5:381391.


Generic image for table
Table 1

Antigens with identified functionsa

Citation: Andersen Å, Brennan P. 1994. Proteins and Antigens of , p 307-332. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch21
Generic image for table
Table 2

Antigens with known sequences but without identified functiona

Citation: Andersen Å, Brennan P. 1994. Proteins and Antigens of , p 307-332. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch21

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error