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. 1995 Oct;102(1):53–57. doi: 10.1111/j.1365-2249.1995.tb06635.x

Human T cell responses to peptide epitopes of the 16-kD antigen in tuberculosis.

G Friscia 1, H M Vordermeier 1, G Pasvol 1, D P Harris 1, C Moreno 1, J Ivanyi 1
PMCID: PMC1553349  PMID: 7554399

Abstract

The 16-kD protein constituent of the Mycobacterium tuberculosis complex has been known mainly for its prominent serological immunogenicity and species specificity in tuberculous infection. In this study, we evaluated the T cell immune repertoire in 27 sensitized healthy subjects and 46 patients with active tuberculosis using 14 overlapping 20mer peptides spanning the entire sequence of this protein. Four of the tested peptides individually stimulated proliferation of blood mononuclear cells from more than 50% of healthy controls. Tuberculosis patients reacted to a narrower peptide range and with a 17-27% lower rate of responses to the four most immunogenic peptides, but these differences do not distinguish in any simple way between the T cell repertoire of patients and sensitized healthy subjects. The most immunogenic peptide (91-110) was recognized by 67% of healthy subjects and by 50% of tuberculosis patients. Importantly, several non-responders to this peptide were stimulated with the other three most permissive peptides with sequences of 111-130, 71-91 and 21-40, resulting in an overall response rate to at least one of these four peptides of 93% in healthy controls and 74% in tuberculosis patients. In view of this additive effect between the most immunogenic peptides, their combined use may achieve sufficient sensitivity in a test aimed at the specific discrimination between infected and non-infected healthy subjects. The major interest in testing with these peptides rests in their species specificity, which is not achieved using purified protein derivative (PPD).

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Selected References

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  1. Booth R. J., Williams D. L., Moudgil K. D., Noonan L. C., Grandison P. M., McKee J. J., Prestidge R. L., Watson J. D. Homologs of Mycobacterium leprae 18-kilodalton and Mycobacterium tuberculosis 19-kilodalton antigens in other mycobacteria. Infect Immun. 1993 Apr;61(4):1509–1515. doi: 10.1128/iai.61.4.1509-1515.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bothamley G. H., Beck J. S., Potts R. C., Grange J. M., Kardjito T., Ivanyi J. Specificity of antibodies and tuberculin response after occupational exposure to tuberculosis. J Infect Dis. 1992 Jul;166(1):182–186. doi: 10.1093/infdis/166.1.182. [DOI] [PubMed] [Google Scholar]
  3. Bothamley G. H., Rudd R., Festenstein F., Ivanyi J. Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis. Thorax. 1992 Apr;47(4):270–275. doi: 10.1136/thx.47.4.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bothamley G., Udani P., Rudd R., Festenstein F., Ivanyi J. Humoral response to defined epitopes of tubercle bacilli in adult pulmonary and child tuberculosis. Eur J Clin Microbiol Infect Dis. 1988 Oct;7(5):639–645. doi: 10.1007/BF01964242. [DOI] [PubMed] [Google Scholar]
  5. Chandramuki A., Bothamley G. H., Brennan P. J., Ivanyi J. Levels of antibody to defined antigens of Mycobacterium tuberculosis in tuberculous meningitis. J Clin Microbiol. 1989 May;27(5):821–825. doi: 10.1128/jcm.27.5.821-825.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Faith A., Moreno C., Lathigra R., Roman E., Fernandez M., Brett S., Mitchell D. M., Ivanyi J., Rees A. D. Analysis of human T-cell epitopes in the 19,000 MW antigen of Mycobacterium tuberculosis: influence of HLA-DR. Immunology. 1991 Sep;74(1):1–7. [PMC free article] [PubMed] [Google Scholar]
  7. Harris D. P., Vordermeier H. M., Friscia G., Román E., Surcel H. M., Pasvol G., Moreno C., Ivanyi J. Genetically permissive recognition of adjacent epitopes from the 19-kDa antigen of Mycobacterium tuberculosis by human and murine T cells. J Immunol. 1993 Jun 1;150(11):5041–5050. [PubMed] [Google Scholar]
  8. Jackett P. S., Bothamley G. H., Batra H. V., Mistry A., Young D. B., Ivanyi J. Specificity of antibodies to immunodominant mycobacterial antigens in pulmonary tuberculosis. J Clin Microbiol. 1988 Nov;26(11):2313–2318. doi: 10.1128/jcm.26.11.2313-2318.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pitchappan R. M. Genetics of tuberculosis susceptibility. Trop Med Parasitol. 1990 Sep;41(3):355–356. [PubMed] [Google Scholar]
  10. Sercarz E. E., Lehmann P. V., Ametani A., Benichou G., Miller A., Moudgil K. Dominance and crypticity of T cell antigenic determinants. Annu Rev Immunol. 1993;11:729–766. doi: 10.1146/annurev.iy.11.040193.003501. [DOI] [PubMed] [Google Scholar]
  11. Surcel H. M., Troye-Blomberg M., Paulie S., Andersson G., Moreno C., Pasvol G., Ivanyi J. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens. Immunology. 1994 Feb;81(2):171–176. [PMC free article] [PubMed] [Google Scholar]
  12. Verbon A., Hartskeerl R. A., Moreno C., Kolk A. H. Characterization of B cell epitopes on the 16K antigen of Mycobacterium tuberculosis. Clin Exp Immunol. 1992 Sep;89(3):395–401. doi: 10.1111/j.1365-2249.1992.tb06969.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Verbon A., Hartskeerl R. A., Schuitema A., Kolk A. H., Young D. B., Lathigra R. The 14,000-molecular-weight antigen of Mycobacterium tuberculosis is related to the alpha-crystallin family of low-molecular-weight heat shock proteins. J Bacteriol. 1992 Feb;174(4):1352–1359. doi: 10.1128/jb.174.4.1352-1359.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Vordermeier H. M., Harris D. P., Friscia G., Román E., Surcel H. M., Moreno C., Pasvol G., Ivanyi J. T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope of the 38-kDa antigen in patients with active disease. Eur J Immunol. 1992 Oct;22(10):2631–2637. doi: 10.1002/eji.1830221024. [DOI] [PubMed] [Google Scholar]
  15. Vordermeier H. M., Harris D. P., Lathigra R., Roman E., Moreno C., Ivanyi J. Recognition of peptide epitopes of the 16,000 MW antigen of Mycobacterium tuberculosis by murine T cells. Immunology. 1993 Sep;80(1):6–12. [PMC free article] [PubMed] [Google Scholar]

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