Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope

The Journal of Immunology : Official Journal of the American Association of Immunologists
Denise S M BoulangerTim Elliott

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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Citations

Mar 13, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiaohua ChenGuoqing Zang
Aug 13, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Malgorzata Anna GarstkaSebastian Springer
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Apr 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Henrik N KløverprisPhilip J Goulder
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Jul 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takayuki KanasekiNilabh Shastri

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