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Infection and Immunity, January 2009, p. 141-151, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00729-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

T-Cell Responses to the Trypanosome Variant Surface Glycoprotein Are Not Limited to Hypervariable Subregions

Taylor R. Dagenais,¹ Karen P. Demick,¹ James D. Bangs,² Katrina T. Forest,¹ Donna M. Paulnock,² and John M. Mansfield^1*

Departments of Bacteriology,¹ Medical Microbiology and Immunology, Microbial Sciences Building, 1550 Linden Drive, University of Wisconsin—Madison, Madison, Wisconsin 53706²

Received 9 June 2008/ Returned for modification 13 July 2008/ Accepted 13 October 2008

Variable subregions within the variant surface glycoprotein (VSG) coat displayed by African trypanosomes are predicted sites for T- and B-cell recognition. Hypervariable subregion 1 (HV-1) is localized to an internal amphipathic alpha helix in VSG monomers and may have evolved due to selective pressure by host T-cell responses to epitopes within this subregion. The prediction of T-cell receptor-reactive sites and major histocompatibility complex class II binding motifs within the HV-1 subregion, coupled with the conservation of amino acid residues in other regions of the molecule sufficient to maintain secondary and tertiary VSG structure, prompted us to test the hypothesis that Th cells may preferentially recognize HV-1 subregion peptides. Thus, we examined the fine specificity of VSG-specific T-cell lines, T-cell hybridomas, and Th cells activated during infection. Our results demonstrate that T-cell epitopes are distributed throughout the N-terminal domain of VSG but are not clustered exclusively within HV-1 or other hypervariable subregions. In contrast, T-cell-reactive sites were not detected within the relatively conserved C-terminal domain of VSG. Overall, this study is the first to dissect the fine specificity of T-cell responses to the trypanosome VSG and suggests that evolution of a conserved HV-1 region may be unrelated to selective pressures exerted by host T-cell responses. This study also demonstrates that T cells do not recognize the relatively invariant C-terminal region of the VSG molecule during infection, suggesting that it could serve as a potential subunit vaccine to provide variant cross-specific immunity for African trypanosomiasis.

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* Corresponding author. Mailing address: Department of Bacteriology, Microbial Sciences Building, 1550 Linden Drive, University of Wisconsin-Madison, Madison, WI 53706. Phone: (608) 262-2596. Fax: (608) 262-9282. E-mail: mansfield{at}bact.wisc.edu

Published ahead of print on 20 October 2008.

Editor: J. F. Urban, Jr.

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Infection and Immunity, January 2009, p. 141-151, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00729-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Dagenais, T. R., Freeman, B. E., Demick, K. P., Paulnock, D. M., Mansfield, J. M. (2009). Processing and Presentation of Variant Surface Glycoprotein Molecules to T Cells in African Trypanosomiasis. J. Immunol. 183: 3344-3355 [Abstract] [Full Text]