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Infection and Immunity, February 2000, p. 848-860, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Comparative Analysis of Antibody Responses against HSP60, Invariant Surface Glycoprotein 70, and Variant Surface Glycoprotein Reveals a Complex Antigen-Specific Pattern of Immunoglobulin Isotype Switching during Infection by Trypanosoma brucei

Magdalena Radwanska,1,* Stefan Magez,2 Alain Michel,3 Benoît Stijlemans,2 Maurice Geuskens,1 and Etienne Pays1

Laboratory of Molecular Parasitology, IBMM, Free University of Brussels ULB, 6041 Gosselies,1 Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology---Free University of Brussels VUB, 1640 Sint Genesius Rode,2 and Department of Biological Chemistry, Faculty of Science, University of Mons-Hainaut, 7000 Mons,3 Belgium

Received 2 July 1999/Returned for modification 31 August 1999/Accepted 28 October 1999

During Trypanosoma brucei infections, the response against the variant surface glycoprotein (VSG) of the parasite represents a major interaction between the mammalian host immune system and the parasite surface. Since immune recognition of other parasite derived factors also occurs, we examined the humoral host response against trypanosome heat shock protein 60 (HSP60), a conserved antigen with an autoimmune character. During experimental T. brucei infection in BALB/c mice, the anti-HSP60 response was induced when parasites differentiated into stumpy forms. This response was characterized by a stage-specific immunoglobulin isotype switching as well as by the induction of an autoimmune response. Specific recognition of trypanosome HSP60 was found to occur during the entire course of infection. Immunoglobulin G2a (IgG2a) and IgG2b antibodies, induced mainly in a T-cell-independent manner, were observed during the first peak of parasitemia, whereas IgG1 and IgG3 antibodies were found at the end of the infection, due to a specific T-cell-mediated response. Comparative analysis of the kinetics of anti-HSP60, anti-invariant surface glycoprotein 70 (ISG70), and anti-VSG antibody responses indicated that the three trypanosome antigens give rise to specific and independent patterns of immunoglobulin isotype switching.


* Corresponding author. Mailing address: Laboratory of Molecular Parasitology, IBMM, Free University of Brussels, Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium. Phone: 32-2-650.97.59. Fax: 32-2-650.97.50. E-mail: mradwans{at}dbm.ulb.ac.be.


Infection and Immunity, February 2000, p. 848-860, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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