Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens.
Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens.
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免疫蛋白酶体塑造抗病毒CD8（+）T细胞在T细胞库水平和病毒抗原的表现下的免疫主导层次结构。
DOI：
10.1084/jem.193.11.1319
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发表时间：
2001-06-04
影响因子：
15.3
通讯作者：
Bennink, J R
中科院分区：
文献类型：
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作者：
Chen, W;Norbury, C C;Cho, Y;Yewdell, J W;Bennink, J R
脊椎动物表达三个细胞因子诱导的蛋白酶体亚基，它们被整合到其结构性合成的对应物的位置。越来越多的证据表明，含有这些亚单位的蛋白酶体(免疫蛋白酶体)产生的多肽不同于标准蛋白酶体产生的多肽。在这项研究中，我们使用缺乏一个免疫蛋白酶体亚基(LMP2)的小鼠来表明，免疫蛋白酶体在建立CD8+T细胞(TCD8+)对流感病毒七个已定义决定簇的免疫优势等级中起着重要作用。在LMP2−/−小鼠中，对两个最主要决定因素的反应急剧下降，而对两个次要决定因素的反应大大增强。过继转移实验表明，一个决定簇(PA224-233)的免疫原性降低可以归因于抗原提呈细胞(APC)的生成减少，而另一个决定簇(NP366-374)的免疫原性降低是由于TCD8+谱系的改变，而不是像以前报道的那样，与LMP2−/−APC产生决定簇的能力降低有关。对其中一个次要决定因素(PB1F262-70)的增强反应与LMP2−/−病毒感染细胞产生的增加相关。这些发现表明，免疫蛋白酶体除了对外来抗原的呈递有影响外，还通过改变TCD8+反应谱系来影响TCD8+反应。
Vertebrates express three cytokine-inducible proteasome subunits that are incorporated in the place of their constitutively synthesized counterparts. There is increasing evidence that the set of peptides generated by proteasomes containing these subunits (immunoproteasomes) differs from that produced by standard proteasomes. In this study, we use mice lacking one of the immunoproteasome subunits (LMP2) to show that immunoproteasomes play an important role in establishing the immunodominance hierarchy of CD8+ T cells (TCD8+) responding to seven defined determinants in influenza virus. In LMP2−/− mice, responses to the two most dominant determinants drop precipitously, whereas responses to two subdominant determinants are greatly enhanced. Adoptive transfer experiments with naive normal and transgenic TCD8+ reveal that the reduced immunogenicity of one determinant (PA224–233) can be attributed to decreased generation by antigen presenting cells (APCs), whereas the other determinant (NP366–374) is less immunogenic due to alterations in the TCD8+ repertoire, and not, as reported previously, to the decreased capacity of LMP2−/− APCs to generate the determinant. The enhanced response to one of the subdominant determinants (PB1F262–70) correlates with increased generation by LMP2− /− virus–infected cells. These findings indicate that in addition to their effects on the presentation of foreign antigens, immunoproteasomes influence TCD8+ responses by modifying the repertoire of responding TCD8+.