title: Trypanosomes expressing a mosaic variant surface glycoprotein coat escape early detection by the immune system.
abstract: Host resistance to African trypanosomiasis is partially dependent on an early and strong T-independent B-cell response against the variant surface glycoprotein (VSG) coat expressed by trypanosomes. The repetitive array of surface epitopes displayed by a monotypic surface coat, in which identical VSG molecules are closely packed together in a uniform architectural display, cross-links cognate B-cell receptors and initiates T-independent B-cell activation events. However, this repetitive array of identical VSG epitopes is altered during the process of antigenic variation, when former and nascent VSG proteins are transiently expressed together in a mosaic surface coat. Thus, T-independent B-cell recognition of the trypanosome surface coat may be disrupted by the introduction of heterologous VSG molecules into the coat structure. To address this hypothesis, we transformed Trypanosoma brucei rhodesiense LouTat 1 with the 117 VSG gene from Trypanosoma brucei brucei MiTat 1.4 in order to produce VSG double expressers; coexpression of the exogenous 117 gene along with the endogenous LouTat 1 VSG gene resulted in the display of a mosaic VSG coat. Results presented here demonstrate that the host's ability to produce VSG-specific antibodies and activate B cells during early infection with VSG double expressers is compromised relative to that during infection with the parental strain, which displays a monotypic coat. These findings suggest a previously unrecognized mechanism of immune response evasion in which coat-switching trypanosomes fail to directly activate B cells until coat VSG homogeneity is achieved. This process affords an immunological advantage to trypanosomes during the process of antigenic variation.
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, 1925 Willow Drive, Madison, WI 53706, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Dubois
authors.forename: Karen P
authors.initials: KP
authors.lastname: Demick
authors.forename: John M
authors.initials: JM
authors.lastname: Mansfield
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000940:Antigenic Variation; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D014170:Transformation, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D016833:Trypanosoma brucei rhodesiense / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000276:immunology / Q000469:parasitology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000913:Antibodies, Protozoan; D014643:Variant Surface Glycoproteins, Trypanosoma