Chapatte Laurence, Ayyoub Maha, Morel Sandra, Peitrequin Anne-Lise, Lévy Nicole, Servis Catherine, Van den Eynde Benoît J, Valmori Danila, Lévy Frédéric
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Cancer Res. 2006 May 15;66(10):5461-8. doi: 10.1158/0008-5472.CAN-05-4310.
Dendritic cells are unique in their capacity to process antigens and prime naive CD8(+) T cells. Contrary to most cells, which express the standard proteasomes, dendritic cells express immunoproteasomes constitutively. The melanoma-associated protein Melan-A(MART1) contains an HLA-A2-restricted peptide that is poorly processed by melanoma cells expressing immunoproteasomes in vitro. Here, we show that the expression of Melan-A in dendritic cells fails to elicit T-cell responses in vitro and in vivo because it is not processed by the proteasomes of dendritic cells. In contrast, dendritic cells lacking immunoproteasomes induce strong anti-Melan-A T-cell responses in vitro and in vivo. These results suggest that the inefficient processing of self-antigens, such as Melan-A, by the immunoproteasomes of professional antigen-presenting cells prevents the induction of antitumor T-cell responses in vivo.
树突状细胞在处理抗原和激活初始CD8(+) T细胞的能力方面独具特色。与大多数表达标准蛋白酶体的细胞不同，树突状细胞组成性地表达免疫蛋白酶体。黑色素瘤相关蛋白Melan-A（MART1）含有一个受HLA-A2限制的肽段，在体外，表达免疫蛋白酶体的黑色素瘤细胞对其处理能力较差。在此，我们表明，Melan-A在树突状细胞中的表达在体外和体内均未能引发T细胞反应，因为它未被树突状细胞的蛋白酶体处理。相反，缺乏免疫蛋白酶体的树突状细胞在体外和体内均可诱导强烈的抗Melan-A T细胞反应。这些结果表明，专业抗原呈递细胞的免疫蛋白酶体对自身抗原（如Melan-A）的低效处理会阻碍体内抗肿瘤T细胞反应的诱导。
