Bloodstream form Trypanosome plasma membrane proteins: antigenic variation and invariant antigens.

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB21GA, UK.
Parasitology (Impact Factor: 2.35). 12/2010; 137(14):2029-39. DOI: 10.1017/S0031182009992034
Source: PubMed

ABSTRACT Trypanosoma brucei is exposed to the adaptive immune system and complement in the blood of its mammalian hosts. The aim of this review is to analyse the role and regulation of the proteins present on the external face of the plasma membrane in the long-term persistence of an infection and transmission. In particular, the following are addressed: (1) antigenic variation of the variant surface glycoprotein (VSG), (2) the formation of an effective VSG barrier shielding invariant surface proteins, and (3) the rapid uptake of VSG antibody complexes combined with degradation of the immunoglobulin and recycling of the VSG.

  • Source
    • "In some forms of the parasite found in the host, the dense surface coat, composed mainly of a homogeneous layer of the parasite's variable surface protein, triggers an efficient antibody response. The continuous and complete replacement of these molecules by another immunologically distinct variable surface protein leads to prolonged infection (Prucca and Lujan 2009; Schwede and Carrington 2010; Tembo and Montgomery 2010; Recker et al. 2011). Here, we observed that VSG, VSP, and VAR are significantly enriched with repeats compared with the proteomes (fig. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Proteins containing repetitive amino acid domains are widespread in all life forms. In parasitic organisms, proteins containing repeats play important roles such as cell adhesion and invasion and immune evasion. Therefore, extracellular and intracellular parasites are expected to be under different selective pressures regarding the repetitive content in their genomes. Here, we investigated whether there is a bias in the repetitive content found in the predicted proteomes of 6 exclusively extracellular and 17 obligate intracellular protozoan parasites, as well as 4 free-living protists. We also attempted to correlate the results with the distinct ecological niches they occupy and with distinct protein functions. We found that intracellular parasites have higher repetitive content in their proteomes than do extracellular parasites and free-living protists. In intracellular parasites, these repetitive proteins are located mainly at the parasite surface or are secreted and are enriched in amino acids known to be part of N-and O-glycosylation sites. Furthermore, in intracellular parasites, the developmental stages that are able to invade host cells express a higher proportion of proteins with perfect repeats relative to other life cycle stages, and these proteins have molecular functions associated with cell invasion. In contrast, in extracellular parasites, degenerate repetitive motifs are enriched in proteins that are likely to play roles in evading host immune response. Altogether, our results support the hypothesis that both the ability to invade host cells and to escape the host immune response may have shaped the expansion and maintenance of perfect and degenerate repeats in the genomes of intra-and extracellular parasites.
    Molecular Biology and Evolution 01/2013; 30(4):951-963. DOI:10.1093/molbev/mst001 · 14.31 Impact Factor
  • Source
    • "It has been estimated that only 30% of nascent VSG 221 attains the native state; the remainder is recognised to be the ER quality control system and is degraded by the proteosome (Field et al. 2007). The trypanosome has monoallelic expression of VSGs and switches the identity of the expressed VSG occasionally, usually as a result of a gene conversion event (reviewed in Schwede and Carrington 2010). It is likely that different VSGs fold at different rates, but the absence of a UPR would indicate that the trypanosome cannot compensate for slow-folding VSGs by increasing chaperone concentrations. "
    [Show abstract] [Hide abstract]
    ABSTRACT: All organisms are able to modulate gene expression in response to internal and external stimuli. Trypanosomes represent a group that diverged early during the radiation of eukaryotes and do not utilise regulated initiation of transcription by RNA polymerase II. Here, the mechanisms present in trypanosomes to alter gene expression in response to stress and change of host environment are discussed and contrasted with those operating in yeast and cultured mammalian cells.
    Protoplasma 05/2011; 249(2):223-38. DOI:10.1007/s00709-011-0282-5 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A methodology for the evolutionary construction of fuzzy rule-based (FRB) models is proposed in the paper. The resulting models are transparent and existing expert knowledge could easily be incorporated into the model. An additional advantage of the model is represented by the economy in computational effort in generating the model output. A new encoding mechanism is used that allows the fuzzy model rule base structure and parameters to be estimated from training data without establishing the complete rule list. It uses rule indices and therefore significantly reduces the computational load. The rules are extracted from the data without using a priori information about the inherent model structure. It makes FRB models as flexible as other types of 'black-box' models (neural networks, polynomial models etc.) and in the same time significantly more transparent, especially when only small subset of all possible rules is considered. This approach is applied to modelling of components of heating ventilating and air-conditioning (HVAC) systems. The FRB models have potential applications in simulation, control and fault detection and diagnosis
    Industrial Electronics Society, 2000. IECON 2000. 26th Annual Confjerence of the IEEE; 02/2000