Absence of Tapasin Alters Immunodominance against a Lymphocytic Choriomeningitis Virus Polytope

作者:Boulanger Denise S M; Oliveira Roberta; Ayers Lisa; Prior Stephen H; James Edward; Williams Anthony P; Elliott Tim*
来源:The Journal of Immunology, 2010, 184(1): 73-83.
DOI:10.4049/jimmunol.0803489

摘要

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. The Journal of Immunology, 2010, 184: 73-83.

  • 出版日期2010-1-1