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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Autophagy and intracellular surveillance: Modulating MHC class Ⅱ antigen presentation with stress
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Autophagy and intracellular surveillance: Modulating MHC class Ⅱ antigen presentation with stress

机译：自噬和细胞内监视：调节应激状态下的MHCⅡ类抗原呈递

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MHC class Ⅰ and Ⅱ proteins selectively acquire peptides from self and foreign antigens for display to T lymphocytes. The spectrum of peptides displayed by class Ⅰ and Ⅱ proteins is critical for self-tolerance as well as the development of immunity against invasive pathogens and tumors. Traditionally, immunologists held that class Ⅰ and Ⅱ molecules were restricted in surveying distinct subcellular domains for ligands. With this model, endogenous antigens processed in the cytosol give rise to peptides for MHC class Ⅰ presentation to cytotoxic T cells, whereas engulfed exogenous antigens degraded in endo-somes and lysosomes are destined for MHC class Ⅱ presentation to CD4~+ T lymphocytes. However, alternative pathways for delivering exogenous antigens to MHC class Ⅰ molecules have now been characterized (1). Similarly, biochemical and functional studies indicate that MHC class Ⅱ molecules display peptides from cytoplasmic proteins for CD4~+ T cell recognition with potential relevance to viral immunity, tumor immunity, and autoimmunity (2). Therefore, defining the specific mechanism(s) by which MHC class Ⅱ molecules in en-dosomal and lysosomal compartments access peptides derived from intracellular antigens within the cytoplasm and nucleus has become a priority. Recent studies using specific viral and bacterial antigens as well as an autoantigen point to three possible pathways: bulk autoph-agy (3, 4), chaperone-mediated autoph-agy (5), and a TAP-dependent pathway (6). In this issue of PNAS, Dengjel et al. (7) take a different approach to this same problem, examining how the induction of aurophagy alters the complex spectrum of peptides displayed by MHC class Ⅱ molecules. Using serum starvation of human B-lymphoblasts to induce autophagy for different time periods, the authors demonstrate notable changes in the peptides associated with class Ⅱ molecules. Remarkably, these authors also demonstrate that the induction of autophagy by starvation alters the balance of active proteases within lysosomes.
机译：MHCⅠ和Ⅱ类蛋白从自身和外来抗原中选择性地提取肽，以展示给T淋巴细胞。 Ⅰ类和Ⅱ类蛋白显示的肽谱对于自我耐受以及对抗侵袭性病原体和肿瘤的免疫力的发展至关重要。传统上，免疫学家认为，在调查不同的亚细胞结构域的配体时，会限制Ⅰ和Ⅱ类分子。在该模型中，胞浆中加工的内源性抗原产生向细胞毒性T细胞呈递M​​HCⅠ类的肽，而吞噬的内体和溶酶体中降解的吞噬的外源性抗原则呈递MHCⅡ类呈递给CD4〜+ T淋巴细胞。然而，现在已经表征了将外源抗原传递到MHCⅠ类分子的替代途径（1）。类似地，生化和功能研究表明，MHCⅡ类分子展示了胞浆蛋白中的肽用于CD4〜+ T细胞识别，与病毒免疫，肿瘤免疫和自身免疫有关（2）。因此，确定内体和溶酶体区室中的MHCⅡ类分子访问细胞质和细胞核内细胞内抗原衍生肽的具体机制已成为当务之急。最近使用特异性病毒和细菌抗原以及自身抗原的研究指出了三种可能的途径：大量自噬（3、4），伴侣介导的自噬（5）和TAP依赖性途径（6）。在本期PNAS中，Dengjel等人。 （7）对这个问题采取了不同的方法，研究了自噬的诱导如何改变由MHCⅡ类分子展示的肽的复杂光谱。利用人类B淋巴母细胞的血清饥饿诱导不同时间段的自噬，作者证明了与Ⅱ类分子相关的肽的显着变化。值得注意的是，这些作者还证明了通过饥饿诱导自噬会改变溶酶体内活性蛋白酶的平衡。

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