Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope
Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope
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.
73-83
Boulanger, Denise S.M.
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Oliveira, Roberta
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Ayres, Lisa
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Prior, Stephen H.
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James, Edward
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Williams, Anthony P.
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Elliott, Tim
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1 January 2010
Boulanger, Denise S.M.
c226ad99-9c9a-485a-b480-42fb8799120f
Oliveira, Roberta
ec397a8f-6319-4847-94b1-72b061d914c3
Ayres, Lisa
3a8968e7-2ca1-4aa3-b1d6-c1dcc404ca25
Prior, Stephen H.
395e9846-78e9-41e7-9edb-e9f80e3ba82f
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Williams, Anthony P.
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
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), .
(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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Accepted/In Press date: 30 November 2009
Published date: 1 January 2010
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 73379
URI: http://eprints.soton.ac.uk/id/eprint/73379
ISSN: 0022-1767
PURE UUID: 57e16a63-61b6-4045-9c69-f82922182f3d
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Date deposited: 05 Mar 2010
Last modified: 14 Mar 2024 02:51
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Author:
Denise S.M. Boulanger
Author:
Roberta Oliveira
Author:
Lisa Ayres
Author:
Stephen H. Prior
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