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Gene Review

Tb927.4.2070  -  antigenic protein

Trypanosoma brucei brucei TREU927

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Disease relevance of Tb927.4.2070

  • Trypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, evades the host immune response through the process of antigenic variation [1].
  • Fluctuating parasitemias resulting from sequential growth of different variable antigenic types occurred subsequently, and these mice died with a median survival time of 48 days [2].
  • The spectrin-like proteins with apparent molecular weights of 180 and 200 share homology with spectrin band 1, since V8-protease from Staphylococcus aureus generated similarly sized, antigenic peptides from these proteins [3].
  • This article reviews the molecular genetic data pertaining to the major surface glycoprotein (MSG) gene family of Pneumocystis carinii and its role in surface variation and compares this fungal system to antigenic variation systems in the protozoan Trypanosoma brucei and the bacteria Borrelia spp [4].
  • Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond [5].

High impact information on Tb927.4.2070

  • In the ETat 1 strain this character was associated with antigenic variation, since expression of the ETat 1.10 variant surface glycoprotein was required to generate resistant (R) clones [6].
  • In each clone, antigenic switching involved interaction between two telomeric members of the AnTat 1.1 multigene family, which share extensive homology throughout their coding regions [7].
  • Thus antigenic variation in trypanosomes is accomplished by sequence variation, not gross structural alteration; the extensive sequence differences among VSGs may be required for another reason, such as the avoidance of recognition by helper T cells [8].
  • These data indicate that minichromosomes contain or can acquire all the DNA sequences necessary in cis for VSG gene expression and antigenic switching [9].
  • Sequences homologous to variant antigen mRNA spliced leader in Trypanosomatidae which do not undergo antigenic variation [10].

Biological context of Tb927.4.2070


Anatomical context of Tb927.4.2070

  • These results show that flagellar tubulin differs from tubulin of other locations in the same cell by at least one antigenic determinant which could be involved in microtubule specialization [16].
  • The ubiquitous phenomenon of glycosylphosphatidylinositol-anchoring of eukaryotic plasma membrane proteins and RNA trans-splicing (trypanosome genes contain no introns), which adds an identical leader sequence to all trypanosome mRNAs, were first defined during studies of antigenic variation [17].
  • Trypanosomes use antigenic variation of their variant-specific surface glycoprotein (VSG) coat as defense against the host immune system [18].
  • T cell responses to the VSG molecule during infection appear to be anatomically compartmentalized and exhibit evidence of clonal maturation (cytokine production) but not clonal expansion (proliferation) after antigenic stimulation [19].
  • Pathogenic trypanosomes undergo antigenic variation, whereby the glycoprotein molecules constituting the cell coat are changed, the parasite thus evading the host's immune response [20].

Associations of Tb927.4.2070 with chemical compounds

  • The cultured trypanosomes had all the characteristics of the in vivo bloodstream forms including: morphology, infectivity, antigenic variation and glucose metabolism [21].
  • Effect of 3-aminobenzamide on antigenic variation of Trypanosoma brucei [22].
  • The conversion can be monitored by loss of [3H] myristic acid incorporated into the diacylglycerol of the glycophosphatidylinositol membrane anchor of the protein, but does not lead to the exposure of the antigenic determinant in the polar head group of the glycolipid [23].
  • The variant antigenic type of each clone was characterized serologically and by 1-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis [24].

Other interactions of Tb927.4.2070


Analytical, diagnostic and therapeutic context of Tb927.4.2070

  • Genetic transformation of trypanosomes and the high efficiency of gene targeting provide new opportunities to investigate the regulation of antigenic variation [17].
  • After treatment with this lipase, the putative precursor can be immunoprecipitated by antibodies directed against the C-terminal cross-reactive antigenic determinant of the VSG [28].
  • Competition radioimmunoassays were carried out between these antisera and nine monoclonal antibodies specific for MITat 1.6 variant surface glycoprotein, which have previously been characterised and shown to recognise five antigenic determinants of which only one is exposed on the surface of the living trypanosome [29].
  • The characterization of antigenic proteins by Western blotting showed that the antibodies recognized the 200-kD and 160-kD proteins of neurofilament (NF) [30].
  • We hypothesize that the development of immunosuppression increases the effectiveness of antigenic variation as an escape mechanism [31].


  1. An analog of myristic acid with selective toxicity for African trypanosomes. Doering, T.L., Raper, J., Buxbaum, L.U., Adams, S.P., Gordon, J.I., Hart, G.W., Englund, P.T. Science (1991) [Pubmed]
  2. Genetics of resistance to the African trypanosomes. VI. Heredity of resistance and variable surface glycoprotein-specific immune responses. De Gee, A.L., Levine, R.F., Mansfield, J.M. J. Immunol. (1988) [Pubmed]
  3. Spectrin-like proteins in the paraflagellar rod structure of Trypanosoma brucei. Schneider, A., Lutz, H.U., Marugg, R., Gehr, P., Seebeck, T. J. Cell. Sci. (1988) [Pubmed]
  4. Genetics of surface antigen expression in Pneumocystis carinii. Stringer, J.R., Keely, S.P. Infect. Immun. (2001) [Pubmed]
  5. Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats. Gould, S.S., Castro, G.A. Immunology (1994) [Pubmed]
  6. A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Xong, H.V., Vanhamme, L., Chamekh, M., Chimfwembe, C.E., Van Den Abbeele, J., Pays, A., Van Meirvenne, N., Hamers, R., De Baetselier, P., Pays, E. Cell (1998) [Pubmed]
  7. Trypanosoma brucei: the extent of conversion in antigen genes may be related to the DNA coding specificity. Pays, E., Houard, S., Pays, A., Van Assel, S., Dupont, F., Aerts, D., Huet-Duvillier, G., Gomés, V., Richet, C., Degand, P. Cell (1985) [Pubmed]
  8. A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Blum, M.L., Down, J.A., Gurnett, A.M., Carrington, M., Turner, M.J., Wiley, D.C. Nature (1993) [Pubmed]
  9. Expression of a minichromosomal variant surface glycoprotein gene in Trypanosoma brucei. Rothwell, V., Aline, R., Parsons, M., Agabian, N., Stuart, K. Nature (1985) [Pubmed]
  10. Sequences homologous to variant antigen mRNA spliced leader in Trypanosomatidae which do not undergo antigenic variation. Nelson, R.G., Parsons, M., Selkirk, M., Newport, G., Barr, P.J., Agabian, N. Nature (1984) [Pubmed]
  11. Transcription of telomere repeats in protozoa. Rudenko, G., Van der Ploeg, L.H. EMBO J. (1989) [Pubmed]
  12. Telomere interactions may condition the programming of antigen expression in Trypanosoma brucei. Van der Werf, A., Van Assel, S., Aerts, D., Steinert, M., Pays, E. EMBO J. (1990) [Pubmed]
  13. Switching trypanosome coats: what's in the wardrobe? Taylor, J.E., Rudenko, G. Trends Genet. (2006) [Pubmed]
  14. Gene duplication and transposition linked to antigenic variation in Trypanosoma brucei. Pays, E., Van Meirvenne, N., Le Ray, D., Steinert, M. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  15. Gene conversions mediating antigenic variation in Trypanosoma brucei can occur in variant surface glycoprotein expression sites lacking 70-base-pair repeat sequences. McCulloch, R., Rudenko, G., Borst, P. Mol. Cell. Biol. (1997) [Pubmed]
  16. A subpopulation of trypanosome microtubules recognized by a monoclonal antibody to tubulin. Gallo, J.M., Anderton, B.H. EMBO J. (1983) [Pubmed]
  17. Antigenic variation in trypanosomes: secrets surface slowly. Cross, G.A. Bioessays (1996) [Pubmed]
  18. A conserved flagellar pocket exposed high mannose moiety is used by African trypanosomes as a host cytokine binding molecule. Magez, S., Radwanska, M., Stijlemans, B., Xong, H.V., Pays, E., De Baetselier, P. J. Biol. Chem. (2001) [Pubmed]
  19. Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. Schleifer, K.W., Filutowicz, H., Schopf, L.R., Mansfield, J.M. J. Immunol. (1993) [Pubmed]
  20. Capping of variable antigen on Trypanosoma brucei, and its immunological and biological significance. Barry, J.D. J. Cell. Sci. (1979) [Pubmed]
  21. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. Baltz, T., Baltz, D., Giroud, C., Crockett, J. EMBO J. (1985) [Pubmed]
  22. Effect of 3-aminobenzamide on antigenic variation of Trypanosoma brucei. Cornelissen, A.W., Michels, P.A., Borst, P., Spanjer, W., Versluijs-Broers, J.A., Van der Meer, C., Farzaneh, F., Shall, S. Biochem. Pharmacol. (1985) [Pubmed]
  23. Identification of an acid-lipase in human serum which is capable of solubilizing glycophosphatidylinositol-anchored proteins. de Almeida, M.L., Turner, M.J., Stambuk, B.B., Schenkman, S. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  24. Characterization of human serum-resistant and serum-sensitive clones from a single Trypanosoma brucei gambiense parental clone. Ortiz, J.C., Sechelski, J.B., Seed, J.R. J. Parasitol. (1994) [Pubmed]
  25. Mismatch repair regulates homologous recombination, but has little influence on antigenic variation, in Trypanosoma brucei. Bell, J.S., McCulloch, R. J. Biol. Chem. (2003) [Pubmed]
  26. The presence of rotenone-sensitive NADH dehydrogenase in the long slender bloodstream and the procyclic forms of Trypanosoma brucei brucei. Beattie, D.S., Howton, M.M. Eur. J. Biochem. (1996) [Pubmed]
  27. Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation. Proudfoot, C., McCulloch, R. Nucleic Acids Res. (2005) [Pubmed]
  28. Identification of a glycolipid precursor of the Trypanosoma brucei variant surface glycoprotein. Krakow, J.L., Hereld, D., Bangs, J.D., Hart, G.W., Englund, P.T. J. Biol. Chem. (1986) [Pubmed]
  29. Mapping of antigenic determinants within peptides of a variant surface glycoprotein of Trypanosoma brucei. Miller, E.N., Allan, L.M., Turner, M.J. Mol. Biochem. Parasitol. (1984) [Pubmed]
  30. Detection and characterization of autoantibodies directed against neurofilament proteins in human African trypanosomiasis. Ayed, Z., Brindel, I., Bouteille, B., Van Meirvenne, N., Doua, F., Houinato, D., Dumas, M., Jauberteau, M.O. Am. J. Trop. Med. Hyg. (1997) [Pubmed]
  31. Immune response to minor variant antigen types (VATs) in a mixed VAT infection of the African trypanosomes. Seed, J.R., Sechelski, J.B. Parasite Immunol. (1988) [Pubmed]
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