A highly polymorphic family of GPI-anchored surface antigens in Toxo with evidence of developmental regulation

Infect Immun. 2007 Oct 15; [Epub ahead of print]

A highly polymorphic family of GPI-anchored surface antigens in Toxoplasma gondii with evidence of developmental regulation

Pollard AM, Onatolu KN, Hiller L, Haldar K, Knoll LJ

Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611.

The life cycle of the apicomplexan parasite Toxoplasma gondii requires that an infectious cyst develop and be maintained throughout the life of the host. The molecules displayed on the parasite surface are important in controlling the immune response to the parasite. T. gondii has a superfamily of glycosylphosphatidylinositol (GPI)-anchored surface antigens termed the SAG (surface antigen) and SAG-related surface antigens (SRS) that are developmentally regulated during infection. Using a clustering algorithm, we identified a new family of 31 surface proteins that are predicted to be GPI-anchored, but are unrelated to the SAG proteins, thus we named these proteins SAG Unrelated Surface Antigens (SUSA). Analysis of the single nucleotide polymorphism density shows that the members of this family are the most polymorphic genes within the T. gondii genome. Immunofluorescence of SUSA1 and SUSA2, two members of the family, revealed that they are found on the parasite surface. We confirmed that SUSA1 and SUSA2 are GPI anchored by phospholipase cleavage. Analysis of expressed sequence tags (ESTs) revealed that SUSA1 had 22 out of 23 ESTs from chronic infection. Analysis of mRNA and protein confirm that SUSA1 is highly expressed in the chronic form of the parasite. Serum from mice with a chronic T. gondii infection reacts to SUSA1, indicating that SUSA1 interacts with the host immune system during infection. This group of proteins likely represents a new family of polymorphic GPI-anchored surface antigens that are recognized by the host's immune system and whose expression is regulated during infection.

PMID: 17938221 [PubMed - as supplied by publisher]