Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jan 1;90(1):188–192. doi: 10.1073/pnas.90.1.188

Selection of T lymphocytes bearing limited T-cell receptor beta chains in the response to a human pathogen.

X H Wang 1, J D Ohmen 1, K Uyemura 1, T H Rea 1, M Kronenberg 1, R L Modlin 1
PMCID: PMC45625  PMID: 8419921

Abstract

Delayed-type hypersensitivity (DTH) is a classic measure of T-cell responsiveness to foreign antigen. To estimate the extent of the T-cell repertoire in the DTH response to a human pathogen, we measured T-cell receptor (TCR) beta-chain variable-region (V beta) gene usage in reversal reactions in leprosy. Reversal reactions represent naturally occurring DTH responses in leprosy, in which augmentation of T-cell responses to Mycobacterium leprae is concomitant with clearance of bacilli from lesions. T cells using the V beta 6-, V beta 12-, V beta 14-, and V beta 19-encoded TCRs were strikingly overrepresented in the lesions of patients as compared to blood and pre-DTH lesions from the same individuals. Furthermore, these data indicate a possible association between the predominant expression of a V beta gene segment in lesions and the major histocompatibility complex class II haplotype of the individual. V beta 6 was prominent in the lesions of four patients who were DR15, a marker of resistance in leprosy infection. Sequence analysis of V beta 6 TCRs showed frequent use of V beta 6.1 and J beta 2.7 gene segments and a conserved amino acid motif in the V-J junction in a reversal-reaction lesion, but not in blood from the same patient. The limited TCR repertoire expressed by the infiltrating T cells suggests that a limited set of antigens is recognized in the DTH response to a human pathogen. We suggest that the mechanism by which major histocompatibility complex haplotype influences DTH in this disease involves the presentation of specific peptides, with subsequent selection of specific TCRs followed by local oligoclonal expansion.

Full text

PDF
188

Images in this article

Selected References

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

  1. Barnetson R. S., Bjune G., Pearson J. M., Kronvall G. Cell mediated and humoral immunity in "reversal reactions". Int J Lepr Other Mycobact Dis. 1976 Jan-Jun;44(1-2):267–274. [PubMed] [Google Scholar]
  2. Ben-Nun A., Liblau R. S., Cohen L., Lehmann D., Tournier-Lasserve E., Rosenzweig A., Zhang J. W., Raus J. C., Bach M. A. Restricted T-cell receptor V beta gene usage by myelin basic protein-specific T-cell clones in multiple sclerosis: predominant genes vary in individuals. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2466–2470. doi: 10.1073/pnas.88.6.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bjune G., Barnetson R. S., Ridley D. S., Kronvall G. Lymphocyte transformation test in leprosy; correlation of the response with inflammation of lesions. Clin Exp Immunol. 1976 Jul;25(1):85–94. [PMC free article] [PubMed] [Google Scholar]
  4. Bloom B. R., Mehra V. Immunological unresponsiveness in leprosy. Immunol Rev. 1984 Aug;80:5–28. doi: 10.1111/j.1600-065x.1984.tb00493.x. [DOI] [PubMed] [Google Scholar]
  5. Bloom B. R. Vaccines for the Third World. Nature. 1989 Nov 9;342(6246):115–120. doi: 10.1038/342115a0. [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Cooper C. L., Mueller C., Sinchaisri T. A., Pirmez C., Chan J., Kaplan G., Young S. M., Weissman I. L., Bloom B. R., Rea T. H. Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. J Exp Med. 1989 May 1;169(5):1565–1581. doi: 10.1084/jem.169.5.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Danska J. S., Livingstone A. M., Paragas V., Ishihara T., Fathman C. G. The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides. J Exp Med. 1990 Jul 1;172(1):27–33. doi: 10.1084/jem.172.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davies T. F., Martin A., Concepcion E. S., Graves P., Cohen L., Ben-Nun A. Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease. N Engl J Med. 1991 Jul 25;325(4):238–244. doi: 10.1056/NEJM199107253250404. [DOI] [PubMed] [Google Scholar]
  10. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  11. DerSimonian H., Band H., Brenner M. B. Increased frequency of T cell receptor V alpha 12.1 expression on CD8+ T cells: evidence that V alpha participates in shaping the peripheral T cell repertoire. J Exp Med. 1991 Sep 1;174(3):639–648. doi: 10.1084/jem.174.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
  13. Godal T., Myrvang B., Samuel D. R., Ross W. F., Lofgren M. Mechanism of "reactions" in borderline tuberculoid (BT) leprosy. A preliminary report. Acta Pathol Microbiol Scand Suppl. 1973;236(0):45–53. [PubMed] [Google Scholar]
  14. Imberti L., Sottini A., Spagnoli G., Primi D. Expression of the human V beta 8 gene product preferentially correlates with class II major histocompatibility complex restriction specificity. Eur J Immunol. 1990 Dec;20(12):2817–2819. doi: 10.1002/eji.1830201244. [DOI] [PubMed] [Google Scholar]
  15. Kotzin B. L., Karuturi S., Chou Y. K., Lafferty J., Forrester J. M., Better M., Nedwin G. E., Offner H., Vandenbark A. A. Preferential T-cell receptor beta-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9161–9165. doi: 10.1073/pnas.88.20.9161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Modlin R. L., Gebhard J. F., Taylor C. R., Rea T. H. In situ characterization of T lymphocyte subsets in the reactional states of leprosy. Clin Exp Immunol. 1983 Jul;53(1):17–24. [PMC free article] [PubMed] [Google Scholar]
  17. Morel P. A., Livingstone A. M., Fathman C. G. Correlation of T cell receptor V beta gene family with MHC restriction. J Exp Med. 1987 Aug 1;166(2):583–588. doi: 10.1084/jem.166.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oksenberg J. R., Stuart S., Begovich A. B., Bell R. B., Erlich H. A., Steinman L., Bernard C. C. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. doi: 10.1038/345344a0. [DOI] [PubMed] [Google Scholar]
  19. Paliard X., West S. G., Lafferty J. A., Clements J. R., Kappler J. W., Marrack P., Kotzin B. L. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 1991 Jul 19;253(5017):325–329. doi: 10.1126/science.1857971. [DOI] [PubMed] [Google Scholar]
  20. Rea T. H., Taylor C. R. Serum and tissue lysozyme in leprosy. Infect Immun. 1977 Dec;18(3):847–856. doi: 10.1128/iai.18.3.847-856.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ridley D. S. Histological classification and the immunological spectrum of leprosy. Bull World Health Organ. 1974;51(5):451–465. [PMC free article] [PubMed] [Google Scholar]
  22. Schurr E., Morgan K., Gros P., Skamene E. Genetics of leprosy. Am J Trop Med Hyg. 1991 Apr;44(4 Pt 2):4–11. doi: 10.4269/ajtmh.1991.44.4. [DOI] [PubMed] [Google Scholar]
  23. Uyemura K., Deans R. J., Band H., Ohmen J., Panchamoorthy G., Morita C. T., Rea T. H., Modlin R. L. Evidence for clonal selection of gamma/delta T cells in response to a human pathogen. J Exp Med. 1991 Sep 1;174(3):683–692. doi: 10.1084/jem.174.3.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Van Kerckhove C., Russell G. J., Deusch K., Reich K., Bhan A. K., DerSimonian H., Brenner M. B. Oligoclonality of human intestinal intraepithelial T cells. J Exp Med. 1992 Jan 1;175(1):57–63. doi: 10.1084/jem.175.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waters M. F., Turk J. L., Wemambu S. N. Mechanisms of reactions in leprosy. Int J Lepr Other Mycobact Dis. 1971 Apr-Jun;39(2):417–428. [PubMed] [Google Scholar]
  26. Wucherpfennig K. W., Ota K., Endo N., Seidman J. G., Rosenzweig A., Weiner H. L., Hafler D. A. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990 May 25;248(4958):1016–1019. doi: 10.1126/science.1693015. [DOI] [PubMed] [Google Scholar]
  27. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
  28. Yamamura M., Wang X. H., Ohmen J. D., Uyemura K., Rea T. H., Bloom B. R., Modlin R. L. Cytokine patterns of immunologically mediated tissue damage. J Immunol. 1992 Aug 15;149(4):1470–1475. [PubMed] [Google Scholar]
  29. de Vries R. R. Genetic control of immunopathology induced by Mycobacterium leprae. Am J Trop Med Hyg. 1991 Apr;44(4 Pt 2):12–16. doi: 10.4269/ajtmh.1991.44.12. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES