Cancer Research UK Centre, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
J Immunol. 2010 Jan 1;184(1):73-83. doi: 10.4049/jimmunol.0803489. Epub 2009 Nov 30.
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.
Tapasin 通过有利于 MHC I 分子上慢脱靶肽的加载来编辑呈递给 CD8(+)T 细胞的肽库。为了研究 tapasin 在 T 细胞免疫优势中的作用，我们使用表达具有不同脱靶率的淋巴细胞性脉络丛脑膜炎病毒表位多聚体的痘病毒病毒载体。在 tapasin 缺陷小鼠中，对亚优势的快速脱靶肽的反应明显受到青睐。这种 CD8(+)T 细胞优势级序的改变是 tapasin 编辑的结果，而不是 tapasin 缺陷小鼠 T 细胞库改变的结果，因为骨髓嵌合小鼠（用 tapasin 敲除骨髓重建的野生型受体）表现出与 tapasin 敲除小鼠相同的优势级序。因此，tapasin 编辑是免疫优势现象的一个促成因素。尽管 tapasin 敲除细胞表面 MHC I 表达水平较低，但 Ag 呈递效率高，导致涉及具有增加功能亲和力的 T 细胞的强烈 T 细胞反应。因此，在该模型中，tapasin 缺陷小鼠没有减少而是改变了免疫反应。
