Bania Jacek, Gatti Evelina, Lelouard Hugues, David Alexandre, Cappello Fanny, Weber Ekkehard, Camosseto Voahirana, Pierre Philippe
Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université de la Méditérranée, Campus de Luminy, Case 906, France.
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6664-9. doi: 10.1073/pnas.1131604100. Epub 2003 May 14.
MHC class II-restricted antigen presentation plays a central role in the immune response against exogenous antigens. The association of invariant (Ii) chain with MHC class II dimers is required for proper antigen presentation to CD4+ T cells by antigen-presenting cells. MHC class II complexes first traffic through the endocytic pathway to allow Ii chain degradation and antigenic peptide loading before their arrival at the cell surface. In recent years, a considerable effort has been directed toward the identification of proteases responsible for Ii chain degradation. Targeted gene deletion in mice has allowed a precise description of the cysteine proteases involved in the last step of Ii chain degradation. By using nonspecialized cellular models expressing MHC II molecules, we are now exploring the contribution of known cysteine proteases to human Ii chain processing. Surprisingly and contrary to the situation in mouse, cathepsin S was found to be the only human cysteine protease able to efficiently degrade the Ii-p10 fragment in epithelial cells. This selectivity has implications for thymic selection and indicates that differences between man and mice are probably more profound at this level than expected.
MHC II类分子限制性抗原呈递在针对外源性抗原的免疫反应中起核心作用。抗原呈递细胞向CD4+ T细胞正确呈递抗原需要恒定链（Ii）与MHC II类二聚体结合。MHC II类复合物首先通过内吞途径运输，以便在到达细胞表面之前使Ii链降解并加载抗原肽。近年来，人们投入了大量精力来鉴定负责Ii链降解的蛋白酶。小鼠中的靶向基因缺失使得能够精确描述参与Ii链降解最后一步的半胱氨酸蛋白酶。通过使用表达MHC II分子的非特异性细胞模型，我们现在正在探索已知半胱氨酸蛋白酶对人Ii链加工的作用。令人惊讶的是，与小鼠的情况相反，组织蛋白酶S被发现是唯一能够有效降解上皮细胞中Ii-p10片段的人半胱氨酸蛋白酶。这种选择性对胸腺选择有影响，表明人与小鼠在这一水平上的差异可能比预期的更为深刻。
