Immune defects in 28-kDa proteasome activator γ-deficient mice
Immune defects in 28-kDa proteasome activator γ-deficient mice
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DOI：
10.4049/jimmunol.172.6.3948
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Monaco, JJ
中科院分区：
文献类型：
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作者：
Barton, LF;Runnels, HA;Monaco, JJ
28-kDa蛋白酶体激活剂（PA 28）家族的蛋白质复合物激活蛋白酶体并可改变蛋白酶体切割特异性。初步研究已经证明了IFN-γ诱导的PA 28 α/β复合物在Ag加工中的作用。尽管不可诱导且主要在核内的PA 28 gamma复合物与影响蛋白酶体依赖性信号通路（例如有丝分裂细胞周期的控制）有关，但之前没有证据表明该结构在银加工中的作用。因此，我们产生了PA 28 γ缺陷小鼠，并研究了它们的免疫功能。PA 28 γ（-/-）小鼠显示CD 8（+）T细胞数量轻微减少，并且不能有效清除肺部真菌感染。然而，两种病毒感染模型中的T细胞应答在识别的抗原表位的幅度和层次上都是正常的。我们的结论是，PA 28 γ（-/-）小鼠，如PA 28 α（-/-）/β（-/-）小鼠，是缺乏在处理只有特定的抗原。
Protein complexes of the 28-kDa proteasome activator (PA28) family activate the proteasome and may alter proteasome cleavage specificity. Initial investigations have demonstrated a role for the IFN-gamma-inducible PA28alpha/beta complex in Ag processing. Although the noninducible and predominantly nuclear PA28gamma complex has been implicated in affecting proteasome-dependent signaling pathways, such as control of the mitotic cell cycle, there is no previous evidence demonstrating a role for this structure in Ag processing. We therefore generated PA28gamma-deficient mice and investigated their immune function. PA28gamma(-/-) mice display a slight reduction in CD8(+) T cell numbers and do not effectively clear a pulmonary fungal infection. However, T cell responses in two viral infection models appear normal in both magnitude and the hierarchy of antigenic epitopes recognized. We conclude that PA28gamma(-/-) mice, like PA28alpha(-/-)/beta(-/-) mice, are deficient in the processing of only specific Ags.