Asparagine deamidation perturbs antigen presentation on class II major histocompatibility complex molecules
Asparagine deamidation perturbs antigen presentation on class II major histocompatibility complex molecules
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DOI：
10.1074/jbc.m501241200
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发表时间：
2005-05-06
影响因子：
4.8
通讯作者：
Watts, C
中科院分区：
文献类型：
--
作者：
Moss, CX;Matthews, SP;Watts, C
翻译后蛋白质修饰可以被B和T淋巴细胞识别，并且可以潜在地使“自身”-蛋白质对免疫系统来说看起来是外来的。这样的修饰可以直接影响加工肽的主要组织相容性复合物限制性T细胞识别，或者可以干扰产生这样的肽的加工事件。使用破伤风毒素C片段蛋白作为一个测试案例，我们表明，自发脱酰胺的天冬酰胺残基干扰处理的酶天冬酰胺内肽酶（AEP），并有助于减少抗原呈递。当AEP靶向的天冬酰胺残基被修饰时，脱酰胺直接抑制AEP作用，或当相邻的Asn残基被脱酰胺时，脱酰胺间接抑制AEP作用。因此，长寿命自身蛋白的脱酰胺可能定性或定量地影响展示给T细胞的自身肽的谱，从而可能导致自身免疫性疾病的发作或恶化。
Post-translational protein modifications can be recognized by B and T lymphocytes and can potentially make "self"-proteins appear foreign to the immune system. Such modifications may directly affect major histocompatibility complex-restricted T cell recognition of processed peptides or may perturb the processing events that generate such peptides. Using the tetanus toxin C fragment protein as a test case, we show that spontaneous deamidation of asparagine residues interferes with processing by the enzyme asparagine endopeptidase (AEP) and contributes to diminished antigen presentation. Deamidation inhibits AEP action either directly, when asparagine residues targeted by AEP are modified, or indirectly, when adjacent Asn residues are deamidated. Thus, deamidation of long-lived self-proteins may qualitatively or quantitatively affect the spectrum of self-peptides displayed to T cells and may thereby contribute to the onset or exacerbation of autoimmune disease.