Hostname: page-component-54dcc4c588-sdd8f Total loading time: 0 Render date: 2025-09-22T01:43:18.543Z Has data issue: false hasContentIssue false
  • English
  • Français

Trypanosome sociology and antigenic variation

Published online by Cambridge University Press:  06 April 2009

K. Vickerman
K. Vickerman
Affiliation:
Department of Zoology, University of Glasgow, Glasgow G12 8QQ
Get access Rights & Permissions [Opens in a new window]

Summary

Survival of the trypanosome (Trypanosoma brucei) population in the mammalian body depends upon paced stimulation of the host's humoral immune response by different antigenic variants and serial sacrifice of the dominant variant (homotype) so that minority variants (heterotypes) can continue the infection and each become a homotype in its turn. New variants are generated by a spontaneous switch in gene expression so that the trypanosome puts on a surface coat of a glycoprotein differing in antigenic specificity from its predecessor. Homotypes appear in a characteristic order for a given trypanosome clone but what determines this order and the pacing of homotype generation so that the trypanosome does not quickly exhaust its repertoire of variable antigens, is not clear. The tendency of some genes to be expressed more frequently than others may reflect the location within the genome and mode of expression of the genes concerned and may influence homotype succession. Differences in the doubling time of different variants or in the rate at which trypanosomes belonging to a particular variant differentiate into non-dividing (vector infective) stumpy forms have also been invoked to explain how a heterotype's growth characteristics may determine when it becomes a homotype. Recent estimations of the frequency of variable antigen switching in trypanosome populations after transmission through the tsetse fly vector, however, suggest a much higher figure (0·97–2·2 × 10−3 switches per cell per generation) than that obtained for syringe-passed infections (10−5–10−7 switches per cell per generation) and it seems probable that most of the variable antigen genes are expressed as minority variable antigen types very early in the infection. Instability of expression is a feature of trypanosome clones derived from infective tsetse salivary gland (metacyclic) trypanosomes and it is suggested that high switching rates in tsetse-transmitted infections may delay the growth of certain variants to homotype status until later in the infection.

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.)

Article purchase

Temporarily unavailable

References

REFERENCES

Aline, R. Jr., Macdonald, G., Brown, E., Allison, J., Myler, P. J., Rothwell, V. & Stuart, K. (1985). (TAA)n within sequences flanking several intrachromosomal variant surface glycoprotein genes in Trypanosoma brucei. Nucleic Acids Research 13, 3161–77.CrossRefGoogle ScholarPubMed
Aline, R. F. J., Scholler, J. K., Nelson, R. G., Agabian, N. & Stuart, K. (1985). Preferential activation of telomeric variant surface glycoprotein gene in Trypanosoma brucei. Molecular and Biochemical Parasitology 17, 311–20.CrossRefGoogle ScholarPubMed
Bancroft, G. J. & Askonas, B. A. (1985). Immunology of African trypanosomes in rodents. In Immunology and Pathogenesis of Trypanosomiasis (ed. Tizard, I.), pp. 75–101. Boca Raton, Florida: CRC Press.Google Scholar
Barry, J. D. (1986). Antigenic variation during Trypanosoma vivax infections of different host species. Parasitology 92, 51–65.CrossRefGoogle ScholarPubMed
Barry, J. D. (1989). African trypanosomiasis. In Vaccination Against Parasitic Diseases, (ed. Lieuw, F. Y.), Boca Raton, Florida: CRC Press. (In the Press).Google Scholar
Barry, J. D., Le Ray, D. & Herbert, W. J. (1979). Infectivity and virulence of Trypanosoma (Trypanozoon) brucei for mice. IV. Dissociation of virulence and variable antigen type in relation to pleomorphism Journal of Comparative Pathology 89, 465–70.CrossRefGoogle ScholarPubMed
Barry, J. D., Crowe, J. S. & Vickerman, K. (1985). Neutralization of individual variable antigen types of metacyclic populations of Trypanosoma brucei does not prevent their subsequent expression in mice. Parasitology 90, 79–88.CrossRefGoogle Scholar
Beale, G. H. (1974). Genetics of antigenic variation in Paramecium: a model system. In Parasites in the Immunized Host. Ciba Foundation Symposium 25 (New Series), pp. 21–33. Amsterdam: Elsevier.CrossRefGoogle Scholar
Bernards, A., Van Der Ploeg, L. H. T., Gibson, W. C., Leewater, P., Eijgenraam, F., De Lange, T., Weijers, P., Calafat, J. & Borst, P. (1986). Rapid change of the repertoire of variant surface glycoprotein genes in trypanosomes by gene duplication and deletion. Journal of Molecular Biology 190, 1–10.CrossRefGoogle ScholarPubMed
Black, S. J., Sendashonga, C. N., Lalor, P. A., Whitelaw, D. D., Jack, R. M., Morrison, W. I. & Murray, M. (1983). Regulation of growth and differentiation of Trypanosoma (Trypanozoon) brucei brucei in resistant (C57B1/6) and susceptible (C3H/He) mice. Parasite Immunology 5, 465–78.CrossRefGoogle Scholar
Black, S. J., Sendashonga, C. N., O'Brien, C., Borony, N. K., Naessens, M., Webster, P. & Murray, M. (1985). Regulation of parasitaemia in mice infected with Trypanosoma brucei. Current Topics in Microbiology and Immunology 117, 93–118.Google ScholarPubMed
Boothroyd, J. C. (1985). Antigenic variation in African trypanosomes. Annual Review of Microbiology 39, 475–502.CrossRefGoogle ScholarPubMed
Borst, P. (1986 a). Discontinuous transcription and antigenic variation in trypanosomes. Annual Review of Biochemistry 55, 701–32.CrossRefGoogle ScholarPubMed
Borst, P. (1986 b). Gene rearrangements controlling gene expression. Biochemistry International 12, 576–91.Google ScholarPubMed
Borst, P. & Cross, G. A. M. (1982). Molecular basis for trypanosome antigenic variation. Cell 29, 291–303.CrossRefGoogle ScholarPubMed
Borst, P. & Greaves, D. R. (1987). Programmed gene arrangements altering gene expression. Science 235, 658–67.CrossRefGoogle Scholar
Capbern, A., Giroud, C., Blatz, T. & Mattern, P. (1977). Trypanosoma equiperdum: étude des variations antigéniques au cours de la trypanosomose expérimentale du lapin. Experimental Parasitology 42, 6–13.CrossRefGoogle Scholar
Clayton, C. E. (1988). The molecular biology of the Kinetoplastidae (sic). In Genetic Engineering (ed. Rigby, P. W. J.), pp. 1–56. London: Academic Press.Google Scholar
Cardosa De Almeida, M. L., Allan, L. M. & Turner, M. J. (1984). Purification and properties of the membrane form of VSGs from Trypanosoma brucei. Journal of Protozoology 31, 53–60.CrossRefGoogle Scholar
Cornelissen, A. W. C. A., Bakkeren, G. A. M., Barry, J. D., Michels, P. A. M. & Borst, P. (1985). Characterization of trypanosome variant antigen genes active in the tsetse fly. Nucleic Acids Research 13, 6441–76.CrossRefGoogle ScholarPubMed
Crowe, J. S., Barry, J. D., Luckins, A. G., Ross, C. A. & Vickerman, K. (1983). All metacyclic variable antigen types of Trypanosoma congolense identified using monoclonal antibodies. Nature, London 306, 389–91.CrossRefGoogle ScholarPubMed
Delauw, M. F., Laurent, M., Paindavoine, P., Aerts, D., Pays, E., Le Ray, D. & Steinert, M. (1987). Characterization of genes coding for two major metacyclic surface antigens in Trypanosoma brucei. Molecular and Biochemical Parasitology 23, 9–17.CrossRefGoogle ScholarPubMed
Delauw, M. F., Pays, E., Steinert, M., Aerts, D., Van Meirvenne, N. & Le Ray, D. (1985). Inactivation and reactivation of a variant-specific antigen gene in cyclically-transmitted Trypanosoma brucei. EMBO Journal 4, 989–93.CrossRefGoogle ScholarPubMed
Dempsey, W. L. & Mansfield, J. M. (1983). Lymphocyte function in experimental African trypanosomiasis. V. Role of antibody and the mononuclear phagocyte system in variant-specific immunity. Journal of Immunology 130, 405–11.CrossRefGoogle ScholarPubMed
Doyle, J. J. (1977). Antigenic variation in the salivarian trypanosomes. In Immunity to Blood Parasites of Animals and Man. (ed. Miller, L. H., Pine, J. A. & McKelvey, J. J.), pp. 31–64. New York: Plenum Press.CrossRefGoogle Scholar
Doyle, J. J., Hirumi, H., Hirumi, K., Lupton, E. N. & Cross, G. A. M. (1980). Antigenic variation in clones of animal-infective Trypanosoma brucei derived and maintained in vitro. Parasitology 80, 359–69.CrossRefGoogle ScholarPubMed
Esser, K. M. & Schoenbechler, J. J. (1985). Expression of two variant surface glycoproteins on individual African trypanosomes during antigen switching. Science 229, 190–3.CrossRefGoogle ScholarPubMed
Gray, A. R. (1965). Antigenic variation in a strain of Trypanosoma brucei transmitted by Glossina morsitans and Glossina palpalis. Journal of General Microbiology 41, 195–214.CrossRefGoogle Scholar
Gray, A. R. (1975). A pattern of development of agglutinogenic antigens of cyclically-transmitted isolates of Trypanosoma gambiense. Transactions of the Royal Society of Tropical Medicine and Hygiene 69, 131–8.CrossRefGoogle ScholarPubMed
Greaves, D. R. & Borst, P. (1987). Trypanosoma brucei variant-specific glycoprotein gene chromatin is sensitive to single-strand-specific endonuclease digestion. Journal of Molecular Biology 197, 471–83.CrossRefGoogle ScholarPubMed
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 glands of Glossina morsitans. Parasitology 83, 595–607.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 63, 609–21.CrossRefGoogle Scholar
Hide, G., Gray, A., Harrison, C. M. & Tait, A. (1989). Identification of an epidermal growth factor receptor homologue in trypanosomes. Molecular and Biochemical Parasitology (In the Press).CrossRefGoogle ScholarPubMed
Inverso, J. A. & Mansfield, J. M. (1983). Genetics of resistance to African trypanosomes. II. Differences in virulence associated with VSSA expression among clones of Trypanosoma rhodesiense. Journal of Immunology 130, 412–17.CrossRefGoogle ScholarPubMed
Inverso, J. A., De Gee, A. L. W. & Mansfield, J. M. (1988). Genetics of resistance to the African trypanosomes. VII. Trypanosome virulence is not linked to variable surface glycoprotein expression. Journal of Immunology 140, 289–93.CrossRefGoogle Scholar
Jackson, J. A. & Fink, G. R. (1981). Gene conversion between duplicated genetic elements in yeast. Nature, London 292, 306–11.CrossRefGoogle ScholarPubMed
Kosinksi, R.J. (1980). Antigenic variation in trypanosomes: a computer analysis of variant order. Parasitology 80, 343–57.Google Scholar
Lamont, G. S., Tucker, R. S. & Cross, G. A. M. (1986). Analysis of antigen switching rates in Trypanosoma brucei. Parasitology 92, 355–67.CrossRefGoogle ScholarPubMed
Laurent, M., Pays, E., Magnus, E., Van Miervenne, N., Matthyssens, G., Williams, R. O. & Steinert, M. (1983). DNA rearrangements linked to expression of a predominant surface antigen gene of trypanosomes. Nature, London 302, 263–6.CrossRefGoogle ScholarPubMed
Laurent, M., Pays, E., Van Der Werf, A., Aerts, D., Magnus, E., Van Meirvenne, N. & Steinert, M. (1984). Translocation alters the activation rate of a trypanosome surface antigen gene. Nucleic Acids Research 12, 8319–28.CrossRefGoogle ScholarPubMed
Lee, M. G. S. & Van Der Ploeg, L. H. T. (1987). Frequent independent duplicative transpositions activate a single VSG gene. Molecular and Cellular Biology 7, 357–64.Google ScholarPubMed
Lenardo, M. J., Esser, K. M., Moon, A. M., Van Der Ploeg, L. H. T. & Donelson, J. E. (1986). Metacyclic variant surface glycoprotein genes of Trypanosoma brucei, subsp. rhodesiense are activated in situ, and their expression is transcriptionally regulated. Molecular and Cellular Biology 6, 1911–17.Google ScholarPubMed
Le Ray, D., Barry, J. D., Easton, C. & Vickerman, K. (1977). First tsetse fly transmission of the ‘AnTat’ serodeme of Trypanosoma brucei. Annates de la Société beige de Médecine Tropicale 57, 369–81.Google ScholarPubMed
Liskay, R. M. & Stachelek, J. L. (1983). Evidence for intrachromosomal gene conversion in cultured mouse cells. Cell 49, 93–102.Google Scholar
Liu, A. Y. C., Michels, P. A. M., Bernards, A. & Borst, P. (1985). Trypanosome variant surface glycoprotein genes expressed early in infection. Journal of Molecular Biology 182, 383–96.CrossRefGoogle ScholarPubMed
Longacre, S. & Eisen, H. (1986). Expression of whole and hybrid genes in Trypanosoma equiperdum antigenic variation EMBO Journal 5, 1057–63.CrossRefGoogle ScholarPubMed
Macaskill, J. A., Holmes, P. H., Whitelaw, D. D., McConnell, I., Jennings, F. W. & Urquhart, G. M. (1980). Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. II. Mechanisms in immune animals. Immunology 40, 629–35.Google ScholarPubMed
McLintock, L., Turner, C. M. R. & Vickerman, K. (1988). Evidence that host factors do not control replication rates in pleomorphic Trypanosoma brucei rhodesiense infections. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 940.Google Scholar
Miller, E. N. & Turner, J. J. (1981). Analysis of antigenic types appearing in first relapse populations of clones of Trypanosoma brucei. Parasitology 82, 63–80.CrossRefGoogle ScholarPubMed
Morrison, W. I., Murray, M. & Akol, G. W. O. (1985). Immune responses of cattle to African trypanosomes. In Immunology and Pathogenesis of African Trypanosomiasis (ed. Tizard, I.), pp. 103–31. Boca Raton, Florida: CRC Press.Google Scholar
Myler, P. J., Allen, A. L., Agabian, N. & Stuart, K. (1985). Antigenic variation in clones of Trypanosoma brucei grown in immune deficient mice. Infection and Immunity 47, 684–90.CrossRefGoogle ScholarPubMed
Myler, P., Nelson, R. G., Agabian, N. & Stuart, K. (1984). Two mechanisms of expression of a predominant variant antigen gene of Trypanosoma brucei. Nature, London 309, 292–4.CrossRefGoogle ScholarPubMed
Myler, P. J., Aline, R. F., Scholler, J. K. & Stuart, K. D. (1988). Multiple events associated with antigenic switching in Trypanosoma brucei. Molecular and Biochemical Parasitology 29, 227–42.CrossRefGoogle ScholarPubMed
Pays, E. (1988 a). DNA recombinations and transposition in trypanosomes. In Transposition (ed. Kingsman, A. J., Chater, K. & Kingsman, S. M.). 43rd Sysposium of the Society for General Microbiology, pp. 301–42. Cambridge: Cambridge University Press.Google Scholar
Pays, E. (1988 b). Expression of variant-specific antigen genes in African trypanosomes. Biology of the Cell 64, 121–30.CrossRefGoogle ScholarPubMed
Pays, E., Delauw, M., Van Assels, S., Laurent, M., Vervoort, T., Van Meirvenne, N. & Steinert, M. (1983). Modifications of a Trypanosoma brucei antigen gene repertoire by different DNA recombinational mechanisms. Cell 35, 721–31.CrossRefGoogle ScholarPubMed
Roth, C. W., Longacre, S., Raibaud, A., Baltz, T. & Eisen, H. (1986). The use of incomplete genes for the construction of a Trypanosoma equiperdum variant surface glycoprotein gene. EMBO Journal 5, 1965–70.CrossRefGoogle ScholarPubMed
Sacks, D. L., Bancroft, G. J., Evans, W. H. & Askonas, B. A. (1982). Incubation of trypanosome-derived mitogenic and immunosuppressive products with peritoneal macrophages allows recovery of biological activities from soluble parasite fractions. Infection and Immunity 36, 160–8.CrossRefGoogle ScholarPubMed
Seed, J. R. (1978). Competition among serologically different clones of Trypanosoma brucei gambiense in vivo. Journal of Protozoology 25, 526–9.CrossRefGoogle ScholarPubMed
Seed, J. R. & Sechelski, J. B. (1988). Immune response to minor variant antigen types (VATs) in a mixed VAT infection of the African trypanosomes. Parasite Immunology 10, 569–80.CrossRefGoogle Scholar
Seed, J. R., Edwards, R. & Sechelski, J. (1984). The ecology of antigenic variation. Journal of Protozoology 31, 48–53.CrossRefGoogle ScholarPubMed
Shea, C., Lee, M. G. S. & Van Der Ploeg, L. H. T. (1987). VSG gene 118 is transcribed from a co-transposed po1-I-like promoter. Cell 50, 603–12.CrossRefGoogle Scholar
Tetley, L., Turner, C. M. R., Barry, J. D., Crowe, J. S. & Vickerman, K. (1987). Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy. Journal of Cell Science 87, 363–72.CrossRefGoogle ScholarPubMed
Timmers, H. T. M., De Lange, T., Kooter, J. M. & Borst, P. (1987). Coincident multiple activations of the same surface antigen gene in Trypanosoma brucei. Journal of Molecular Biology 194, 81–90.CrossRefGoogle ScholarPubMed
Turner, C. M. R. & Barry, J. D. (1989). High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Parasitology 99, 67–75.CrossRefGoogle ScholarPubMed
Turner, C. M. R., Barry, J. D. & Vickerman, K. (1986). Independent expression of the metacyclic and bloodstream variable antigen repertoires of Trypanosoma brucei rhodesiense. Parasitology 92, 67–73.CrossRefGoogle ScholarPubMed
Turner, C. M. R., Barry, J. D., Maudlin, I. & Vickerman, K. (1988). An estimate of the size of the metacyclic variable antigen repertoire of Trypanosoma brucei rhodesiense. Parasitology 97, 269–76.Google ScholarPubMed
Turner, C. M. R., Hunter, C. A., Barry, J. D. & Vickerman, K. (1986). Similarity in variable antigen type composition of Trypanosoma brucei rhodesiense populations in different sites within the mouse host. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 824–30.CrossRefGoogle ScholarPubMed
Van Der Ploeg, L. (1987). Control of variant surface antigen switching in trypanosomes. Cell 51, 159–61.CrossRefGoogle ScholarPubMed
Van Meirvenne, N., Janssens, P. G. & Magnus, E. (1975). Antigenic variation in syringe-passaged populations of Trypanosoma (Trypanozoon) brucei. 1. Rationalization of the experimental approach. Annates de la Société belge de Médecine Tropicale 55, 1–23.Google ScholarPubMed
Vickerman, K. (1978). Antigenic variation in trypanosomes. Nature, London 273, 613–17.CrossRefGoogle ScholarPubMed
Vickerman, K. & Barry, J. D. (1982). African trypanosomiasis. In Immunology of Parasitic Infections (ed. Cohen, S. & Warren, K. S.), pp. 204–260. Oxford: Blackwell Scientific Publications.Google Scholar