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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.

Original publication

DOI

10.4049/jimmunol.0803489

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

01/2010

Volume

184

Pages

73 - 83

Addresses

Cancer Research UK Centre, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.

Keywords

CD8-Positive T-Lymphocytes, Animals, Mice, Knockout, Mice, Lymphocytic choriomeningitis virus, Membrane Transport Proteins, Histocompatibility Antigens Class I, Epitopes, T-Lymphocyte, Immunodominant Epitopes, Chromatography, High Pressure Liquid, Lymphocyte Activation, Antigen Presentation