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Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite

Feliu, V and Vasseur, V and Grover, HS and Chu, HH and Brown, MJ and Wang, J and Boyle, JP and Robey, EA and Shastri, N and Blanchard, N (2013) Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite. PLoS Pathogens, 9 (6). ISSN 1553-7366

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Abstract

CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood.Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells. © 2013 Feliu et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Feliu, V
Vasseur, V
Grover, HS
Chu, HH
Brown, MJmjb86@pitt.eduMJB86
Wang, J
Boyle, JPboylej@pitt.eduBOYLEJ0000-0003-0000-9243
Robey, EA
Shastri, N
Blanchard, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorDenkers, Eric Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 June 2013
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 9
Number: 6
DOI or Unique Handle: 10.1371/journal.ppat.1003449
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 01 Jul 2014 16:12
Last Modified: 14 Apr 2018 11:55
URI: http://d-scholarship.pitt.edu/id/eprint/22124

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