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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules
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Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules

机译：两种丰富的蛋白酶体亚型，可独特地处理HLA I类分子呈递的某些抗原

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摘要

Most antigenic peptides presented by MHC class I molecules result from the degradation of intracellular proteins by the proteasome. In lymphoid tissues and cells exposed to IFNγ, the standard proteasome is replaced by the immunoproteasome, in which all of the standard catalytic subunits β1, β2, and β5 are replaced by their in-ducible counterparts β1i, β2i, and β5i, which have different cleavage specificities. The immunoproteasome thereby shapes the repertoire of antigenic peptides. The existence of additional forms of protea-somes bearing a mixed assortment of standard and inducible catalytic subunits has been suggested. Using a new set of unique subunit-specific antibodies, we have now isolated, quantified, and characterized human proteasomes that are intermediate between the standard proteasome and the immunoproteasome. They contain only one ((β5i) or two (β1i and β5i) of the three inducible catalytic subunits of the immunoproteasome. These intermediate proteasomes represent between one-third and one-half of the proteasome content of human liver, colon, small intestine, and kidney. They are also present in human tumor cells and dendritic cells. We identified two tumor antigens of clinical interest that are processed exclusively either by intermediate proteasomes β5i (MAGE-A3_(271-279)) or by intermediate proteasomes β1i-β5i (MAGE-A10_(254-262)). The existence of these intermediate proteasomes broadens the repertoire of antigens presented to CD8 T cells and implies that the antigens presented by a given cell depend on their proteasome content.
机译：MHC I类分子呈递的大多数抗原性肽是由于蛋白酶体降解细胞内蛋白质而产生的。在暴露于IFNγ的淋巴组织和细胞中，标准蛋白酶体被免疫蛋白酶体替代，其中所有标准催化亚基β1，β2和β5均被其诱导型对应物β1，β2i和β5i替代，它们具有不同的切割特异性。免疫蛋白酶体由此塑造抗原肽库。已经提出存在带有混合形式的标准和诱导型催化亚基的蛋白酶体的其他形式。现在，使用一组新的独特的亚基特异性抗体，我们已经分离，定量和表征了人类蛋白酶体，它们介于标准蛋白酶体和免疫蛋白酶体之间。它们仅包含免疫蛋白酶体的三个可诱导催化亚基中的一个（（β5i）或两个（β1i和β5i）），这些中间蛋白酶体占人体肝脏，结肠，小肠的蛋白酶体含量的三分之一至一半，它们还存在于人类肿瘤细胞和树突状细胞中。我们鉴定了两种具有临床意义的肿瘤抗原，它们仅由中间蛋白酶体β5i（MAGE-A3_（271-279））或由中间蛋白酶体β1i-β5i（ MAGE-A10_（254-262））。这些中间蛋白酶体的存在拓宽了呈递给CD8 T细胞的抗原的范围，并暗示给定细胞呈递的抗原取决于它们的蛋白酶体含量。

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  • 作者

    Benoit Guillaume; Jacques Chapiro; Vincent Stroobant; Didier Colau; Benoit Van Holle; Gregory Parvizi; Marie-Pierre Bousquet-Dubouch; Ivan Theate; Nicolas Parmentier; Benott J. Van den Eynde;

  • 作者单位

    Ludwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnInstitut de Pharmacologie et de Biologie Structural, Centre National de la Recherche Scientifique, 31077 Toulouse, France Universite de Toulouse, Universite Paul Sabatier, 31077 Toulouse, France;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

    rnLudwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    antigen processing; antigenic peptide; immunoproteasome; tumor antigen; MAGE;

    机译：抗原加工;抗原肽免疫蛋白酶体肿瘤抗原法师;

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