Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells
Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells
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DOI：
10.4049/jimmunol.166.6.3678
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发表时间：
2001-03-15
影响因子：
4.4
通讯作者：
Zinkernagel, RM
中科院分区：
文献类型：
--
作者：
Ludewig, B;McCoy, K;Zinkernagel, RM
本研究评估了在何种程度上通过DC上的MBC I类分子呈递外源性获得的自身抗原可能有助于自身反应性CTL的激活和随后的自身免疫性疾病的发展。我们通过使用大鼠胰岛素启动子淋巴细胞性脉络丛脑膜炎病毒糖蛋白自身免疫性糖尿病模型显示，在摄取外源性Ag后，DC对自身反应性CTL的激活非常有限，首先是由于体外和体内DC上MHC I类相关肽的半衰期短，其次是由于DC对细胞相关自身Ag的MHC I类呈递相当低效，这两种机制可能是至关重要的，在建立高阈值的诱导自身反应性CTL，防止自身免疫后遗症后释放的隔离和以前的免疫忽略组织抗原。
This study evaluated to what extent presentation of exogenously acquired self-Ags via MBC class I molecules on DC might contribute to the activation of self-reactive CTL and subsequent development of autoimmune disease. We show here by using the rat insulin promotor lymphocytic choriomeningitis virus glycoprotein model of autoimmune diabetes that the activation of self-reactive CTL by DC after uptake of exogenous Ag is very limited, first by the short half-life of MHC class I-associated peptides on DC in vitro and in vivo, and second by the rather inefficient MHC class I presentation of cell-associated self-Ags by DC, These two mechanisms are probably crucial in establishing high thresholds for the induction of self-reactive CTL that prevent autoimmune sequelae after release of sequestered and previously immunologically ignored tissue Ags.