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

• Telomere repeat transcription was found in all seven protozoan species tested, but was alpha-amanitin resistant only in trypanosome species which exhibited antigenic variation [11].
• This suggests that interactions between chromosome ends may precede and favour the rearrangements leading to antigenic variation [12].
• This preponderance of pseudogenes in the VSG gene repertoire will necessitate a rethink of how antigenic variation in African trypanosomes operates [13].
• Gene duplication and transposition linked to antigenic variation in Trypanosoma brucei [14].
• Gene conversions mediating antigenic variation in Trypanosoma brucei can occur in variant surface glycoprotein expression sites lacking 70-base-pair repeat sequences [15].

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

• Mismatch repair regulates homologous recombination, but has little influence on antigenic variation, in Trypanosoma brucei [25].
• The presence of three subunits of NADH dehydrogenase was observed in immunoblots of mitochondrial proteins with specific antibodies raised against peptides corresponding to predicted antigenic regions of these proteins, which provides further evidence for the presence of NADH dehydrogenase [26].
• Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation [27].

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].

References