Summary
Mycobacterium tuberculosis (Mtb) remains a major threat to human health worldwide. Although treatment of infection is an important part of tuberculosis control, an improved vaccine is essential for the elimination of this disease. Control of infection with Mtb is dependent on the cellular immune system, which in turn requires an understanding of those antigens that are capable of stimulating CD4+ and CD8+ T-cell responses. Peptide libraries provide a high-throughput system for identifying novel T-cell epitopes. They can also be used to assess the hierarchy of immunodominance of these novel antigens and epitopes that are associated with infection with Mtb. This T-cell-driven means of antigen discovery is well adapted to vaccine development as well as developing the tools necessary to understand the natural history of this important human pathogen.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Muller, I., Cobbold, S. P., Waldmann, H., and Kaufmann, S. H. (1987) Impaired resis-tance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells. Infect. Immun. 55, 2037–2041.
Flynn, J. L., Goldstein, M. M., Triebold, K. J., Koller, B., and Bloom, B. R. (1992) Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 89, 12013–12017.
Silva, C. L., Silva, M. F., Pietro, R. C., and Lowrie, D. B. (1994) Protection against tuberculosis by passive transfer with T-cell clones recognizing mycobacterial heat-shock protein 65. Immunology 83, 341–346.
Stenger, S., Mazzaccaro, R. J., Uyemura, K., Cho, S., Barnes, P. F., Rosat, J. P., Sette, A., Brenner, M. B., Porcelli, S. A., Bloom, B. R., and Modlin, R. L. (1997) Differential effects of cytolytic T cell subsets on intracellular infection. Science 276, 1684–1687.
Tan, J. S., Canaday, D. H., Boom, W. H., Balaji, K. N., Schwander, S. K., and Rich, E. A. (1997) Human alveolar T lymphocyte responses to Mycobacterium tuberculosis antigens: role for CD4+ and CD8+ cytotoxic T cells and relative resistance of alveolar macrophages to lysis. J. Immunol. 159, 290–297.
Ladel, C. H., Daugelat, S., and Kaufmann, S. H. (1995) Immune response to Mycobacterium bovis Bacille Calmette Guerin infection in major histocompatibility complex class I- and II-deficient knock-out mice: contribution of CD4 and CD8 T cells to acquired resistance. Eur. J. Immunol. 25, 377–384.
Behar, S. M., Dascher, C. C., Grusby, M. J., Wang, C. R., and Brenner, M. B. (1999) Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis. J. Exp. Med. 189, 1973–1980.
Sousa, A. O., Mazzaccaro, R. J., Russell, R. G., Lee, F. K., Turner, O. C., Hong, S., Van Kaer, L., and Bloom, B. R. (2000) Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. Proc. Natl. Acad. Sci. USA 97, 4204–4208.
Rolph, M. S., Raupach, B., Kobernick, H. H., Collins, H. L., Perarnau, B., Lemonnier, F. A., and Kaufmann, S. H. (2001) MHC class Ia-restricted T cells partially account for beta2-microglobulin-dependent resistance to Mycobacterium tuberculosis. Eur. J. Immunol. 31, 1944–1949.
Klein, M. R., Smith, S. M., Hammond, A. S., Ogg, G. S., King, A. S., Vekemans, J., Jaye, A., Lukey, P. T., and McAdam, K. P. (2001) HLA-B*35-restricted T cell epitopes in the antigen 85 complex of Mycobacterium tuberculosis. J. Infect. Dis. 183, 928–934.
Lewinsohn, D. A., Winata, E., Swarbrick, G., Tanner, K. E., Cook, M. S., Null, M. D., Cansler, M. E., Sette, A., Sidney, J., and Lewinsohn, D. M. (2007) Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B. PLoS Pathog. 3, 1240–1249.
Flyer, D. C., Ramakrishna, V., Miller, C., Myers, H., McDaniel, M., Root, K., Flournoy, C., Engelhard, V. H., Canaday, D. H., Marto, J. A., Ross, M. M., Hunt, D. F., Shabano-witz, J., and White, F. M. (2002) Identification by mass spectrometry of CD8(+)-T-cell Mycobacterium tuberculosis epitopes within the Rv0341 gene product. Infect. Immun. 70, 2926–2932.
Charo, J., Geluk, A., Sundback, M., Mirzai, B., Diehl, A. D., Malmberg, K. J., Achoulr, A., Huriguchi, S., van Meijgaarden, K. E., Drijfout, J. W., Beekman, N., van Veelen, P., Ossendorp, F., Ottenhoff, T. H., and Kiessling, R. (2001) The identification of a common pathogen-specific HLA class I A*0201-restricted cytogoxic T cell epitope encoded within the heat shock protein 65. Eur. J. Immunol. 31, 3602–3611.
Dong, Y., Demaria, S., Sun, X., Santori, F. R., Jesdale, B. M., De Groot, A. S., Rom, W. N., and Bushkin, Y. (2004) HLA-A2-restricted CD8+-cytotoxic-T-cell responses to novel epitopes in Mycobacterium tuberculosis superoxide dismutase, alanine dehydrogense, and glutamine synthetatse. Infect. Immun. 72, 2412–2415.
Shams, H., Barnes, P. F., Weis, S. E., Klucar, P., and Wizel, B. (2003) Human CD8+ T cells recognize epitopes of the 28-kDa hemolysin and the 38-kDa antigen of Mycobacterium tuberculosis. J. Leukoc. Biol. 74, 1008–1014.
Lewinsohn, D. A., Lines, R. A., and Lewinsohn, D. M. (2002) Human dendritic cells presenting adenovirally expressed antigen elicit Mtb-specific CD8+ T cells. Am. J. Respir. Crit. Care 166, 843–848.
Geluk, A., van Meijgaarden, K. E., Franken, K. L., Drijfhout, J. W., D’Souza, S., Necker, A., Huygen, K., and Ottenhoff, T. H. (2000) Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans. J. Immunol. 165, 6463–6471.
Caccamo, N., Milano, S., Di Sano, C., Cigna, D., Ivanyi, J., Krensky, A. M., Dieli, F., and Salerno, A. (2002) Identification of epitopes of Mycobacterium tuberculosis 16-kDA protein recognized by human leukocyte antigin-A*0201 CD8(+) T lymphocytes. J. Infect. Dis. 186, 991–998.
Klein, M. R., Hammond, A. S., Smith, S. M., Jaye, A., Lukey, P. T., and McAdam, K. P. (2002) HLA-B*35-restricted CD8(+)-T-cell epitope in Mycobacterium tuberculosis Rv2903c. Infect. Immun. 70, 981–984.
Mohagheghpour, N., Gammon, D., Kawamura, L. M., van Vollenhoven, A., Benike, C. J., and Engleman, E. G. (1998) CTL response to Mycobacterium tuberculosis: identification of an immunogenic epitope in the 19-kDa lipoprotein. J. Immunol. 161, 2400–2406.
Smith, S. M., Brookes, R., Klein, M. R., Malin, A. S., Lukey, P. T., King, A. S., Ogg, G. S., Hill, A. V., and Dockrell, H. M. (2000) Human CD8+ CTL specific for the mycobacterial major secreted antigen 85A. J. Immunol. 165, 7088–7095.
Lewinsohn, D. M., Zhu, L., Madison, V. J., Dillon, D. C., Fling, S. P., Reed, S. G., Grabstein, K. H., and Alderson, M. R. (2001) Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells: definition of antigenic specificity. J. Immunol. 166, 439–446.
Shams, H., Klucar, P., Weis, S. E., Lalvani, A., Moonan, P. K., Safi, H., Wizel, B., Ewer, K., Nepom, G. T., Lewinsohn, D. M., Andersen, P., and Barnes, P. F. (2004) Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles. J. Immunol. 173, 1966–1977.
Lalvani, A., Brookes, R., Wilkinson, R. J., Malin, A. S., Pathan, A. A., Andersen, P., Dockrell, H., Pasvol, G., and Hill, A. V. (1998) Human cytolytic and interferon gamma-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 95, 270–275.
Pathan, A. A., Wilkinson, K. A., Wilkinson, R. J.,Latif, M., McShane, H., Pasvol, G., Hill, A. V., and Lalvani, A. (2000) High frequencies of circulating IFN-gamma-secre-ting CD8 cytotoxic T cells specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in M. tuberculosis-infected subjects without disease. Eur. J. Immunol. 30, 2713–2721.
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., Dolganov, G., Efron, B., Butcher, P. D., Nathan, C., and Schoolnik, G. K. (2003) Transcriptional Adaptation of Mycobacterium tuberculosis within macrophages: Insights into the phagosomal environment. J. Exp. Med. 198, 693–704.
http://genolist.pasteur/tuberculist/.
Lewinsohn, D. M., Briden, A. L., Reed, S. G., Grabstein, K. H., and Alderson, M. R. (2000) Mycobacterium tuberculosis-reactive CD8+ T lymphocytes: the relative contribution of classical versus nonclassical HLA restriction. J. Immunol. 165, 925–930.
Heinzel, A. S., Grotzke, J. E., Lines, R. A., Lewinsohn, D. A., McNabb, A. L., Streblow, D. N., Braud, V. M., Grieser, H. J., Belisle, J. T., and Lewinsohn, D. M. (2002) HLA-E dependent presentation of Mtb-derived antigen to human CD8+ T cells. J. Exp. Med. 196, 1473–1481.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Frieder, M., Lewinsohn, D.M. (2009). T-Cell Epitope Mapping in Mycobacterium tuberculosis Using PepMixes Created by Micro-Scale SPOT™− Synthesis. In: Schutkowski, M., Reineke, U. (eds) Epitope Mapping Protocols. Methods in Molecular Biology™, vol 524. Humana Press. https://doi.org/10.1007/978-1-59745-450-6_27
Download citation
DOI: https://doi.org/10.1007/978-1-59745-450-6_27
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-934115-17-6
Online ISBN: 978-1-59745-450-6
eBook Packages: Springer Protocols