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 (2009) Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope Journal of Immunology, 184, (1), pp. 73-83. (doi:10.4049/jimmunol.0803489).
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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.
|Digital Object Identifier (DOI):||doi:10.4049/jimmunol.0803489|
|Subjects:||Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Date Deposited:||05 Mar 2010|
|Last Modified:||24 Feb 2017 10:41|
Funded by: CRUK (UNSPECIFIED)
UNSPECIFIED to UNSPECIFIED
|Further Information:||Google Scholar|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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