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Immunodominance, competition and evolution in immunological responses to helminth parasite antigens

Published online by Cambridge University Press:  06 April 2009

D. J. Austin  and
R. M. Anderson
D. J. Austin*
Affiliation:
Wellcome Centre for the Epidemiology of Infectious Diseases, University of Oxford, South Parks Road, Oxford OX1 3PS
R. M. Anderson
Affiliation:
Wellcome Centre for the Epidemiology of Infectious Diseases, University of Oxford, South Parks Road, Oxford OX1 3PS
*
*Corresponding author. Tel: 01865 271264. Fax: 01865 281245. E-mail: daren.austin@zoology.ox.ac.uk.
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Summary

The paper describes the development and analysis of a mathematical framework for the study of the within-host population dynamics of the interaction between macroparasites and the human immune system. Simple models of this interaction based on the proliferation of T cell clones specific to parasite antigen, and the impact of clonal expansion on parasite survival, capture the basic features of age-related changes in worm loads within human communities. The model is generalized to multiple epitopes on a single antigen, and reveals competitive exclusion amongst T cells, with a single clone becoming immunodominant in the absence of cross-reactive responses and genetic variation. The introduction of genetic heterogeneity and concomitant variability in the immunogenicity of specific epitopes induces additional complexity into the dynamical interaction. Most importantly, multiple epitope models with antigenic variation suggest that the immunodominant response may not necessarily be targeted at the epitope at which some strains show the greatest immunogenicity. High immunogenicity at a particular epitope can be masked by genetic variability even though many of the variants are more immunogenic at this epitope by comparison with the epitope to which the immunodominant immunological response is directed.

Keywords

antigenic variationhelminth antigensimmunological responsesimmunodominancemathematical models
Type
Research Article
Information
Parasitology , Volume 113 , Issue 2 , August 1996 , pp. 157 - 172
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Anderson, R. M. (1991). Populations and infectious diseases: ecology or epidemiology. Journal of Animal Ecology 60, 1–50.CrossRefGoogle Scholar
Anderson, R. M. (1994 a). The Croonian Lecture, 1994. Populations, infectious disease and immunity: a very nonlinear world. Proceedings of the Royal Society of London, B 346, 457–505.Google ScholarPubMed
Anderson, R. M. (1994 b). Mathematical studies of parasite infection and immunity. Science 264, 1884–1886.CrossRefGoogle ScholarPubMed
Anderson, R. M. & May, R. M. (1991). Infectious Disease of Humans: Dynamics and Control. Oxford: Oxford University Press.CrossRefGoogle Scholar
Bundy, D. A. (1990). Control of intestinal nematode infectious by chemotherapy: mass treatment versus diagnostic screening. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 622–625.CrossRefGoogle Scholar
Butterworth, A. E., Dunne, D. W., Fulford, A. J., Thorne, K. J., Gachuhi, K., Ouma, J. H. & Sturrock, R. F. (1992). Human immunity to S. mansoni: observations on mechanisms and implications for control. Immunological Investigations 21, 391–407.CrossRefGoogle Scholar
Elkins, D. B., Haswell-Elkins, M. & Anderson, R. M. (1986). The epidemiology and control of intestinal helminths in the Pulicat Lake region of Southern India. I. Study designs and pre- and post-treatment observations on Ascaris lumbricoides infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 774–792.CrossRefGoogle Scholar
Hill, A. B., Mullbacher, A. & Blanden, R. V. (1993). Irl genes, peripheral cross-tolerance and immuno-dominance in MHC class 1-restricted T cell responses; an old quagmire revisited. Immunology Review 133, 75–91.CrossRefGoogle Scholar
Jones, K. R., Hickling, J. K., Targett, G. A. & Playfair, J. H. (1990). Polyclonal in vitro proliferation responses from nonimmune donors to Plasmodium falciparum malaria antigens. European Journal of Immunology 20, 307–315.CrossRefGoogle ScholarPubMed
Kelso, A. (1995). Thl and Th2 subsets: paradigms lost? Immunology Today 16, 374–379.CrossRefGoogle Scholar
Maizels, R. M., Bundy, D. A., Selkirk, M. E., Smith, D. F. & Anderson, R. M. (1993). Immunuological modulation and evasion by helminth parasites in human populations. Nature, London 365, 797–805.CrossRefGoogle ScholarPubMed
Matis, L. A., Glimcher, L. H., Paul, W. E. & Schwartz, R. H. (1982). Magnitude of the response of histocompatibility-restricted T cell clones is a function of the product of concentration of antigen and la molecules. Proceedings of the National Academy of Sciences, USA 80, 6019–6023.CrossRefGoogle Scholar
May, R. M. (1973). Stability and Complexity in Model Ecosystems. Princeton University Press, Princeton, USA.Google ScholarPubMed
Mitchell, G. F. (1979). Effector cells, molecules and mechanisms in host-protective immunity to parasites. Immunology 39, 209–223.Google Scholar
Mossman, T. R. & Coffman, R. L. (1989). Heterogeneity of cytokine secretion lead to different functional properties. Annual Review of Immunology 7, 145–173.CrossRefGoogle Scholar
Nowak, M. A., May, R. M., Phillips, R. E., Rowland-Jones, S., Lal-Loo, D., Mcadam, S., Klenerman, P., Sigmund, K., Bangham, C. R. & Mcmichael, A. J. (1995). Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature, London 375, 606–611.CrossRefGoogle ScholarPubMed
Nowak, M. A., May, R. M. & Sigmund, K. (1995). Immune responses against multiple epitopes. Journal of Theoretical Biology 175, 3325–3536.CrossRefGoogle ScholarPubMed
Posnett, D. N., Mcgrath, H. & Tam, J. P. (1988). A novel method for producing anti-peptide antibodies, production of site-specific antibodies to the T cell antigen receptor beta chain. Journal of Biological Chemistry 263, 1719–1725.CrossRefGoogle Scholar
Reynolds, S. R., Dahl, C. & Harn, D. A. (1994). T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase. Journal of Immunology 152, 193–200.CrossRefGoogle Scholar
Reynolds, S. R., Shoemaker, C. B. & Harn, D. A. (1992). T and B cell epitope mapping of SM23, an integral membrane protein of Schistosoma mansoni. Journal of Immunology 149, 3995–4001.CrossRefGoogle Scholar
Schweitzer, A. N. & Anderson, R. M. (1992 a). Dynamic interaction between CD4+ T cells and parasitic helminths: mathematical models of heterogeneity in outcome. Parasitology 105, 513–522.CrossRefGoogle ScholarPubMed
Schweitzer, A. N. & Anderson, R. M. (1992 b). The regulation of immunological responses to parasitic infections and the development of tolerance. Proceedings of the Royal Society of London, B 247, 107–112.Google ScholarPubMed
Sercarz, E., Lehman, P. V., Ametani, A., Benichou, G., Miller, A. & Moudgil, K. (1994). Dominance and crypticity of T cell antigenic determinants. Annual Review of Immunology 11, 729–766.CrossRefGoogle Scholar
Sher, A. & Coffman, R. L. (1992). Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annual Review of Immunology 10, 385–409.CrossRefGoogle Scholar
Townsend, A. & Boomer, H. (1989). Antigen recognition by class 1-restricted T lymphocytes. Annual Review of Immunology 7, 601–624.CrossRefGoogle Scholar
Upatham, E. S., Viyanant, V., Brokelman, W. Y., Kurathong, S., Ardsungnoen, P. & Chindaphol, U. (1992). Predisposition to reinfection by intestinal helminths after chemotherapy in south Thailand. International Journal for Parasitology 22, 801–806.CrossRefGoogle ScholarPubMed
Wynn, T. A., Jankovic, D., Hieny, S., Zioncheck, K., Jardieu, P., Cheever, A. W. & Sher, A. W. (1995). IL 12 exacerbates rather than suppresses T helper 2-dependent pathology in the absence of endogenous IFN-γ. Journal of Immunology 158, 3999–4009.CrossRefGoogle Scholar