Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1989 Sep;57(9):2786–2793. doi: 10.1128/iai.57.9.2786-2793.1989

Immunological characterization of a human homolog of the 65-kilodalton mycobacterial antigen.

A K Dudani 1, R S Gupta 1
PMCID: PMC313527  PMID: 2668187

Abstract

A human mitochondrial protein, designated P1 (63 kilodaltons [kDa], shows extensive sequence homology (47% identical residues and an additional approximately 20% conserved changes) to the 65-kDa mycobacterial antigen. To understand the relationship of these proteins, the cross-reactivity of several monoclonal antibodies directed against the 65-kDa Mycobacterium leprae antigen towards human, Chinese hamster, chicken, and bacterial cells has been examined. A number of antibodies (Y1-2, ML 30-A2, and F47-9-1) were found to cross-react with a 63-kDa antigen in vertebrate cell extracts and stained mitochondria in immunofluorescence studies. Some of these antibodies also reacted with a P1-beta-galactosidase fusion protein in recombinant Escherichia coli cells, expressing part of the human P1 protein. These results provide strong evidence that P1 is the mammalian homolog of the 65-kDa antigen. The human P1 protein also shows significant similarity (P less than 0.001) to a number of other bacterial and viral proteins including the pol polyprotein of human immunodeficiency viruses and the penicillin-binding protein of Neisseria gonorrhoeae. The observed similarity between human P1 protein and the major antigenic proteins of pathogenic organisms (e.g., 60- to 65-kDa mycobacterial antigen) suggests its possible involvement in autoimmune diseases (e.g., rheumatoid arthritis) by antigenic mimicry.

Full text

PDF
2788

Images in this article

2787Image
on p.2787
2789Image
on p.2789
2789Image
on p.2789

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. C., Barry M. E., Buchanan T. M. Exact definition of species-specific and cross-reactive epitopes of the 65-kilodalton protein of Mycobacterium leprae using synthetic peptides. J Immunol. 1988 Jul 15;141(2):607–613. [PubMed] [Google Scholar]
  2. Austen B. M., Haberland M. E., Nyc J. F., Smith E. L. Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. IV. The COOH-terminal 669 residues of the peptide chain; comparison with other glutamate dehydrogenases. J Biol Chem. 1977 Nov 25;252(22):8142–8149. [PubMed] [Google Scholar]
  3. Bahr G. M., Rook G. A., al-Saffar M., Van Embden J., Stanford J. L., Behbehani K. Antibody levels to mycobacteria in relation to HLA type: evidence for non-HLA-linked high levels of antibody to the 65 kD heat shock protein of M. bovis in rheumatoid arthritis. Clin Exp Immunol. 1988 Nov;74(2):211–215. [PMC free article] [PubMed] [Google Scholar]
  4. Buchanan T. M., Nomaguchi H., Anderson D. C., Young R. A., Gillis T. P., Britton W. J., Ivanyi J., Kolk A. H., Closs O., Bloom B. R. Characterization of antibody-reactive epitopes on the 65-kilodalton protein of Mycobacterium leprae. Infect Immun. 1987 Apr;55(4):1000–1003. doi: 10.1128/iai.55.4.1000-1003.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen I. R., Holoshitz J., van Eden W., Frenkel A. T lymphocyte clones illuminate pathogenesis and affect therapy of experimental arthritis. Arthritis Rheum. 1985 Aug;28(8):841–845. doi: 10.1002/art.1780280802. [DOI] [PubMed] [Google Scholar]
  6. Cohen I. R. Regulation of autoimmune disease physiological and therapeutic. Immunol Rev. 1986 Dec;94:5–21. doi: 10.1111/j.1600-065x.1986.tb01161.x. [DOI] [PubMed] [Google Scholar]
  7. Cornelissen B. J., Hooft van Huijsduijnen R. A., Bol J. F. A tobacco mosaic virus-induced tobacco protein is homologous to the sweet-tasting protein thaumatin. 1986 May 29-Jun 4Nature. 321(6069):531–532. doi: 10.1038/321531a0. [DOI] [PubMed] [Google Scholar]
  8. Emmrich F., Thole J., van Embden J., Kaufmann S. H. A recombinant 64 kilodalton protein of Mycobacterium bovis bacillus Calmette-Guerin specifically stimulates human T4 clones reactive to mycobacterial antigens. J Exp Med. 1986 Apr 1;163(4):1024–1029. doi: 10.1084/jem.163.4.1024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gillis T. P., Buchanan T. M. Production and partial characterization of monoclonal antibodies to Mycobacterium leprae. Infect Immun. 1982 Jul;37(1):172–178. doi: 10.1128/iai.37.1.172-178.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gillis T. P., Miller R. A., Young D. B., Khanolkar S. R., Buchanan T. M. Immunochemical characterization of a protein associated with Mycobacterium leprae cell wall. Infect Immun. 1985 Aug;49(2):371–377. doi: 10.1128/iai.49.2.371-377.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gupta R. S., Austin R. C. Mitochondrial matrix localization of a protein altered in mutants resistant to the microtubule inhibitor podophyllotoxin. Eur J Cell Biol. 1987 Dec;45(1):170–176. [PubMed] [Google Scholar]
  12. Gupta R. S., Dudani A. K. Mitochondrial binding of a protein affected in mutants resistant to the microtubule inhibitor podophyllotoxin. Eur J Cell Biol. 1987 Oct;44(2):278–285. [PubMed] [Google Scholar]
  13. Gupta R. S., Ho T. K., Moffat M. R., Gupta R. Podophyllotoxin-resistant mutants of Chinese hamster ovary cells. Alteration in a microtubule-associated protein. J Biol Chem. 1982 Jan 25;257(2):1071–1078. [PubMed] [Google Scholar]
  14. Gupta R. S., Venner T. J., Chopra A. Genetic and biochemical studies with mutants of mammalian cells affected in microtubule-related proteins other than tubulin: mitochondrial localization of a microtubule-related protein. Can J Biochem Cell Biol. 1985 Jun;63(6):489–502. doi: 10.1139/o85-068. [DOI] [PubMed] [Google Scholar]
  15. Hemmingsen S. M., Woolford C., van der Vies S. M., Tilly K., Dennis D. T., Georgopoulos C. P., Hendrix R. W., Ellis R. J. Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature. 1988 May 26;333(6171):330–334. doi: 10.1038/333330a0. [DOI] [PubMed] [Google Scholar]
  16. Holoshitz J., Matitiau A., Cohen I. R. Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II. J Clin Invest. 1984 Jan;73(1):211–215. doi: 10.1172/JCI111193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Husson R. N., Young R. A. Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1679–1683. doi: 10.1073/pnas.84.6.1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jindal S., Dudani A. K., Singh B., Harley C. B., Gupta R. S. Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen. Mol Cell Biol. 1989 May;9(5):2279–2283. doi: 10.1128/mcb.9.5.2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kaufmann S. H., Väth U., Thole J. E., Van Embden J. D., Emmrich F. Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64-kDa protein. Eur J Immunol. 1987 Mar;17(3):351–357. doi: 10.1002/eji.1830170308. [DOI] [PubMed] [Google Scholar]
  20. Kolk A. H., Ho M. L., Klatser P. R., Eggelte T. A., Kuijper S., de Jonge S., van Leeuwen J. Production and characterization of monoclonal antibodies to Mycobacterium tuberculosis, M. bovis (BCG) and M. leprae. Clin Exp Immunol. 1984 Dec;58(3):511–521. [PMC free article] [PubMed] [Google Scholar]
  21. Kurosky A., Markel D. E., Peterson J. W. Covalent structure of the beta chain of cholera enterotoxin. J Biol Chem. 1977 Oct 25;252(20):7257–7264. [PubMed] [Google Scholar]
  22. Lamb J. R., Ivanyi J., Rees A. D., Rothbard J. B., Howland K., Young R. A., Young D. B. Mapping of T cell epitopes using recombinant antigens and synthetic peptides. EMBO J. 1987 May;6(5):1245–1249. doi: 10.1002/j.1460-2075.1987.tb02360.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Matsuda G., Maita T., Umegane T. The primary structure of L-1 light chain of chicken fast skeletal muscle myosin and its genetic implication. FEBS Lett. 1981 Apr 6;126(1):111–113. doi: 10.1016/0014-5793(81)81045-9. [DOI] [PubMed] [Google Scholar]
  24. McMullin T. W., Hallberg R. L. A highly evolutionarily conserved mitochondrial protein is structurally related to the protein encoded by the Escherichia coli groEL gene. Mol Cell Biol. 1988 Jan;8(1):371–380. doi: 10.1128/mcb.8.1.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mehra V., Sweetser D., Young R. A. Efficient mapping of protein antigenic determinants. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7013–7017. doi: 10.1073/pnas.83.18.7013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mustafa A. S., Gill H. K., Nerland A., Britton W. J., Mehra V., Bloom B. R., Young R. A., Godal T. Human T-cell clones recognize a major M. leprae protein antigen expressed in E. coli. Nature. 1986 Jan 2;319(6048):63–66. doi: 10.1038/319063a0. [DOI] [PubMed] [Google Scholar]
  27. Oldstone M. B. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  28. PEARSON C. M. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med. 1956 Jan;91(1):95–101. doi: 10.3181/00379727-91-22179. [DOI] [PubMed] [Google Scholar]
  29. Reading D. S., Hallberg R. L., Myers A. M. Characterization of the yeast HSP60 gene coding for a mitochondrial assembly factor. Nature. 1989 Feb 16;337(6208):655–659. doi: 10.1038/337655a0. [DOI] [PubMed] [Google Scholar]
  30. Shinnick T. M., Sweetser D., Thole J., van Embden J., Young R. A. The etiologic agents of leprosy and tuberculosis share an immunoreactive protein antigen with the vaccine strain Mycobacterium bovis BCG. Infect Immun. 1987 Aug;55(8):1932–1935. doi: 10.1128/iai.55.8.1932-1935.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shinnick T. M. The 65-kilodalton antigen of Mycobacterium tuberculosis. J Bacteriol. 1987 Mar;169(3):1080–1088. doi: 10.1128/jb.169.3.1080-1088.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shinnick T. M., Vodkin M. H., Williams J. C. The Mycobacterium tuberculosis 65-kilodalton antigen is a heat shock protein which corresponds to common antigen and to the Escherichia coli GroEL protein. Infect Immun. 1988 Feb;56(2):446–451. doi: 10.1128/iai.56.2.446-451.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sire J., Auffray C., Jordan B. R. Rat immunoglobulin delta heavy chain gene: nucleotide sequence derived from cloned cDNA. Gene. 1982 Dec;20(3):377–386. doi: 10.1016/0378-1119(82)90206-2. [DOI] [PubMed] [Google Scholar]
  34. Spratt B. G. Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature. 1988 Mar 10;332(6160):173–176. doi: 10.1038/332173a0. [DOI] [PubMed] [Google Scholar]
  35. Stalker D. M., Thomas C. M., Helinski D. R. Nucleotide sequence of the region of the origin of replication of the broad host range plasmid RK2. Mol Gen Genet. 1981;181(1):8–12. doi: 10.1007/BF00338997. [DOI] [PubMed] [Google Scholar]
  36. Thole J. E., Hindersson P., de Bruyn J., Cremers F., van der Zee J., de Cock H., Tommassen J., van Eden W., van Embden J. D. Antigenic relatedness of a strongly immunogenic 65 kDA mycobacterial protein antigen with a similarly sized ubiquitous bacterial common antigen. Microb Pathog. 1988 Jan;4(1):71–83. doi: 10.1016/0882-4010(88)90049-6. [DOI] [PubMed] [Google Scholar]
  37. Thole J. E., Keulen W. J., De Bruyn J., Kolk A. H., Groothuis D. G., Berwald L. G., Tiesjema R. H., van Embden J. D. Characterization, sequence determination, and immunogenicity of a 64-kilodalton protein of Mycobacterium bovis BCG expressed in escherichia coli K-12. Infect Immun. 1987 Jun;55(6):1466–1475. doi: 10.1128/iai.55.6.1466-1475.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Thole J. E., van Schooten W. C., Keulen W. J., Hermans P. W., Janson A. A., de Vries R. R., Kolk A. H., van Embden J. D. Use of recombinant antigens expressed in Escherichia coli K-12 to map B-cell and T-cell epitopes on the immunodominant 65-kilodalton protein of Mycobacterium bovis BCG. Infect Immun. 1988 Jun;56(6):1633–1640. doi: 10.1128/iai.56.6.1633-1640.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tsoulfa G., Rook G. A., Van-Embden J. D., Young D. B., Mehlert A., Isenberg D. A., Hay F. C., Lydyard P. M. Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis. Ann Rheum Dis. 1989 Feb;48(2):118–123. doi: 10.1136/ard.48.2.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vodkin M. H., Williams J. C. A heat shock operon in Coxiella burnetti produces a major antigen homologous to a protein in both mycobacteria and Escherichia coli. J Bacteriol. 1988 Mar;170(3):1227–1234. doi: 10.1128/jb.170.3.1227-1234.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  43. Young D. B., Khanolkar S. R., Barg L. L., Buchanan T. M. Generation and characterization of monoclonal antibodies to the phenolic glycolipid of Mycobacterium leprae. Infect Immun. 1984 Jan;43(1):183–188. doi: 10.1128/iai.43.1.183-188.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Young D., Lathigra R., Hendrix R., Sweetser D., Young R. A. Stress proteins are immune targets in leprosy and tuberculosis. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4267–4270. doi: 10.1073/pnas.85.12.4267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zalkin H., Yanofsky C. Yeast gene TRP5: structure, function, regulation. J Biol Chem. 1982 Feb 10;257(3):1491–1500. [PubMed] [Google Scholar]
  46. van Eden W., Thole J. E., van der Zee R., Noordzij A., van Embden J. D., Hensen E. J., Cohen I. R. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature. 1988 Jan 14;331(6152):171–173. doi: 10.1038/331171a0. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES