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Publication : Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope.

First Author  Boulanger DS Year  2010
Journal  J Immunol Volume  184
Issue  1 Pages  73-83
PubMed ID  19949070 Mgi Jnum  J:159043
Mgi Id  MGI:4441102 Doi  10.4049/jimmunol.0803489
Citation  Boulanger DS, et al. (2010) Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope. J Immunol 184(1):73-83
abstractText  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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