Kincaid Eleanor Z, Murata Shigeo, Tanaka Keiji, Rock Kenneth L
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Nat Immunol. 2016 Aug;17(8):938-45. doi: 10.1038/ni.3480. Epub 2016 Jun 13.
The cells that stimulate positive selection express specialized proteasome β-subunits different from those expressed by all other cells, including those involved in negative selection. Mice that lack all four specialized proteasome β-subunits, and therefore express only constitutive proteasomes in all cells, had a profound defect in the generation of CD8(+) T cells. While a defect in positive selection would reflect an inability to generate the appropriate positively selecting peptides, a block at negative selection would point to the potential need to switch peptides between positive selection and negative selection to avoid the two processes' often cancelling each other out. We found that the block in T cell development occurred around the checkpoints of positive selection and, unexpectedly, negative selection as well.
刺激阳性选择的细胞表达与所有其他细胞（包括参与阴性选择的细胞）所表达的不同的特殊蛋白酶体β亚基。缺乏所有四种特殊蛋白酶体β亚基，因此在所有细胞中仅表达组成型蛋白酶体的小鼠，在CD8(+) T细胞生成方面存在严重缺陷。虽然阳性选择缺陷会反映出无法产生适当的阳性选择肽，但阴性选择受阻则表明可能需要在阳性选择和阴性选择之间切换肽，以避免这两个过程经常相互抵消。我们发现T细胞发育的阻滞发生在阳性选择的检查点附近，而且出乎意料的是，阴性选择的检查点附近也发生了阻滞。
