Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope

Boulanger, Denise S.M., Oliveira, Roberta, Ayres, Lisa, Prior, Stephen H., James, Edward, Williams, Anthony P. and Elliott, Tim (2010) Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope. Journal of Immunology, 184 (1), 73-83. (doi:10.4049/jimmunol.0803489).

Abstract

Tapasin edits the peptide repertoire presented to CD8+ T cells by favoring loading of slow off-rate peptides on MHC I molecules. To investigate the role of tapasin on T cell immunodominance we used poxvirus viral vectors expressing a polytope of lymphocytic choriomeningitis virus epitopes with different off-rates. In tapasin-deficient mice, responses to subdominant fast off-rate peptides were clearly favored. This alteration of the CD8+ T cell hierarchy was a consequence of tapasin editing and not a consequence of the alteration of the T cell repertoire in tapasin-deficient mice, because bone marrow chimeric mice (wild-type recipients reconstituted with tapasin knockout bone marrow) showed the same hierarchy as the tapasin knockout mice. Tapasin editing is therefore a contributing factor to the phenomenon of immunodominance. Although tapasin knockout cells have low MHC I surface expression, Ag presentation was efficient and resulted in strong T cell responses involving T cells with increased functional avidity. Therefore, in this model, tapasin-deficient mice do not have a reduced but rather have an altered immune response.

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Contributors

Author: Denise S.M. Boulanger

Author: Edward James

Author: Tim Elliott

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