Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-23T00:31:11.677Z Has data issue: false hasContentIssue false

The effects of genetic exchange on variable antigen expression in Trypanosoma brucei

Published online by Cambridge University Press:  06 April 2009

C. M. R. Turner
Affiliation:
Laboratory for Biochemical Parasitology, Department of Zoology, University of Glasgow, Glasgow G12 8QQ
N. Aslam
Affiliation:
Laboratory for Biochemical Parasitology, Department of Zoology, University of Glasgow, Glasgow G12 8QQ
E. Smith
Affiliation:
Laboratory for Biochemical Parasitology, Department of Zoology, University of Glasgow, Glasgow G12 8QQ
N. Buchanan
Affiliation:
Wellcome Unit for Molecular Parasitology, Department of Veterinary Parasitology, University of Glasgow, Bearsden Road, Glasgow G61 1QH
A. Tait
Affiliation:
Wellcome Unit for Molecular Parasitology, Department of Veterinary Parasitology, University of Glasgow, Bearsden Road, Glasgow G61 1QH

Extract

The inheritance of variant surface antigens in Trypanosoma brucei has been determined by identifying variable antigen types (VATs) in each of two cloned parental stocks and then examining the presence and abundance of these VATs in hybrid progeny produced when these stocks undergo genetic exchange during co-transmission through tsetse flies. Nine VATs have been identified from the repertoire of the parental stock STIB 247L and 5 VATs have been identified from the parental stock STIB 386AA; the identified VATs were exclusive to each stock. Their inheritance was elucidated using two assays. In the first, repertoire antisera (RAS) containing antibody specificities to many different VATs were raised in rabbits to the 2 parental stocks and 6 progeny clones. The presence of VAT-specific antibodies in these RAS was then determined by antibody-dependent complement-mediated lysis. In the second assay, the 2 parental stocks and 4 hybrid progeny clones were each independently transmitted through tsetse flies and VATs observed using VAT-specific antisera in indirect immunofluorescence of metacyclic trypanosomes and in bloodstream forms of fly-bitten mice. The results from both assays showed that (1) both metacyclic- and bloodstream-VATs were inherited into the progeny, (2) each hybrid progeny clone contained some VATs from both parents, (3) hybrids did not express all the VATs from either parent, (4) there was little apparent pattern as to which VATs had been inherited and which had not and (5) the VAT repertoires of the hybrid progeny appeared to be larger than those of the parents. In addition, two results indicated that control of VAT expression remains unaltered after genetic exchange. Firstly, the immunofluorescence results showed that VATs present in hybrid trypanosomes were expressed at the same stage during an infection and at approximately the same prevalence as in the parent. Secondly, a double-labelling experiment using direct immunofluorescence indicated that individual hybrid trypanosomes did not generally simultaneously express more than one VAT. Taken together, these results demonstrate that recombinant VAT repertoires are created when trypanosomes undergo genetic exchange and that genetic exchange is a mechanism whereby the generation of new serodemes can occur.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1991

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anon. (1978). Proposals for the nomenclature of salivarian trypanosomes and for the maintenance of reference collections. Bulletin of the World Health Organization 56, 467–80.Google Scholar
Barry, J. D., Crowe, J. S. & Vickerman, K. (1983). Instability of the Trypanosoma brucei rhodesiense metacyclic variable antigen repertoire. Nature, London 306, 699701.CrossRefGoogle ScholarPubMed
Barry, J. D. & Turner, C. M. R. (1991). The dynamics of growth and antigenic variation of African trypanosomes. Parasitology Today (in the Press).CrossRefGoogle ScholarPubMed
Capburn, A., Giroud, C., Baltz, T. & Mattern, P. (1977). Trypanosoma equiperdum: Etude des variations antigéniques au cours de la trypanosomose expérimentale du lapin. Experimental Parasitology 42, 613.Google Scholar
Esser, K. M. & Schoenbechler, M. J. (1985). Expression of two variant surface glycoproteins on individual African trypanosomes during antigen switching. Science 229, 190–3.CrossRefGoogle ScholarPubMed
Gibson, W. C. (1989). Analysis of a genetic cross between Trypanosoma brucei rhodesiense and T.b. brucei. Parasitology 99, 391402.CrossRefGoogle ScholarPubMed
Graham, S. V., Matthews, K. R., Shiels, P. G. & Barry, J. D. (1990). Distinct, developmental stage-specific activation mechanisms of trypanosome VSG genes. Parasitology 101, 361–7.CrossRefGoogle ScholarPubMed
Gray, A. R. (1965). Antigenic variation in clones of Trypanosoma brucei. 1. Immunological relationships of the clones. Parasitology 59, 2736.Google Scholar
Hajduk, S. L., Cameron, C. R., Barry, J. D. & Vickerman, K. (1981). Antigenic variation in cyclically transmitted Trypanosoma brucei. Variable antigen type composition of metacyclic trypanosome populations from the salivary gland of Glossina morsitans. Parasitology 83, 595607.CrossRefGoogle Scholar
Hajduk, S. L. & Vickerman, K. (1981). Antigenic variation in cyclically transmitted Trypanosoma brucei. Variable antigen type composition of the first parasitaemia in mice bitten by trypanosome-infected Glossina morsitans. Parasitology 83, 609–21.CrossRefGoogle Scholar
Jenni, L., Marti, S., Schweizer, J., BetschartB., LE B., LE, Page, R. W. F., Wells, J. M., Tait, A., Paindavoine, P., Pays, E. & Steinert, M. (1986). Hybrid formation between African trypanosomes during cyclical transmission. Nature, London 322, 173–5.Google Scholar
Johnstone, A. & Thorpe, R. (1982). Immunochemistry in Practice. Oxford: Blackwell.Google Scholar
Lumsden, W. H. R., Herbert, W. H. & Mcneillage, G. J. C. (1973). Techniques with Trypanosomes. Edinburgh: Churchill Livingstone.Google Scholar
Mccloskey, M. A., Liu, Z. A. & Poo, M. M. (1984). Lateral electromigration and diffusion of Fc receptors on rat basophilic leukemia cells: effects of IgE binding. Journal of Cell Biology 99, 778–87.CrossRefGoogle ScholarPubMed
Maudlin, I. & Dukes, P. (1985). Extrachromosomal inheritance of susceptibility to trypanosome infection in tsetse flies. 1. Selection of susceptible and refractory lines of Glossina morsitans morsitans. Annals of Tropical Medicine and Parasitology 79, 317–24.Google Scholar
Maudlin, I. & Welburn, S. C. (1987). Lectin mediated establishment of midgut infections of Trypanosoma congolense and Trypanosoma brucei in Glossina morsitans. Tropical Medicine and Parasitology 38, 167–70.Google ScholarPubMed
Paindavoine, P., Zampetti-Bosseler, F., Pays, E., Schweizer, J., Guyaux, M., Jenni, L. & Steinert, M. (1986). Trypanosome hybrids generated in tsetse flies by nuclear fusion. The EMBO Journal 5, 3631–6.Google Scholar
Sternberg, J., Turner, C. M. R., Wells, J. M., RANFORD-Cartwright, L. C., Le Page, R. W. F. & Tait, A. (1989). Gene exchange in African trypanosomes: frequency and allelic segregation. Molecular and Biochemical Parasitology 34, 269–80.CrossRefGoogle ScholarPubMed
Tait, A. & Turner, C. M. R. (1990). Genetic exchange in Trypanosoma brucei. Parasitology Today 6, 70–5.Google Scholar
Thon, G., Baltz, T., Giroud, C. & Eisen, H. (1990). Trypanosome variable surface glycoproteins: composite genes and order of expression. Genes and Development 9, 1374–83.CrossRefGoogle Scholar
Turner, C. M. R. (1990). The use of experimental artefacts in African trypanosome research. Parasitology Today 6, 1417.CrossRefGoogle ScholarPubMed
Turner, C. M. R., Sternberg, J., Buchanan, N., Smith, E., Hide, G. & Tait, A. (1990). Evidence that the mechanism of gene exchange in Trypanosoma brucei involves meiosis and syngamy. Parasitology 101, 377–86.CrossRefGoogle ScholarPubMed
Van Der Meer, C., Versluijs-Broers, J. A. M. & Opperdoes, F. R. (1979). Trypanosoma brucei: trypanocidal effect of salicylhydroxamic acid plus glycerol in infected rats. Experimental Parasitology 48, 126–34.Google Scholar
Van Der Ploeg, L. H. T., Valerio, D., De Lange, T., Bernards, A., Borst, P. & Grosveld, F. G. (1982). An analysis of cosmid clones of nuclear DNA from Trypanosoma brucei shows that the genes for variant surface glycoproteins are clustered in the genome. Nucleic Acids Research 10, 5905–23.CrossRefGoogle ScholarPubMed
Van Meirvenne, N., Janssens, P. G. & Magnus, E. (1975). Antigenic variation in syringe-passaged populations of Trypanosoma (Trypanozoon) brucei. I. Rationalization of the experimental approach. Annales de la Société belge de Médecine tropicale 55, 123.Google ScholarPubMed
Van Meirvenne, N., Magnus, E. & Vervoort, T. (1977). Comparisons of variable antigen types produced by trypanosome strains of the subgenus Trypanozoon. Annales de la Société belge de Médecine Tropicale 57, 409–23.Google ScholarPubMed
Welburn, S. C. & Maudlin, I. (1987). A simple in vitro method for infecting tsetse with trypanosomes. Annals of Tropical Medicine and Parasitology 81, 453–5.CrossRefGoogle ScholarPubMed