Moss Catherine X, Matthews Stephen P, Lamont Douglas J, Watts Colin
Division of Cell Biology and Immunology, University of Dundee, Scotland, United Kingdom.
J Biol Chem. 2005 May 6;280(18):18498-503. doi: 10.1074/jbc.M501241200. Epub 2005 Mar 4.
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.
翻译后蛋白质修饰可被B淋巴细胞和T淋巴细胞识别，并有可能使“自身”蛋白质在免疫系统看来像是外来的。此类修饰可能直接影响主要组织相容性复合体限制的T细胞对加工后肽段的识别，或者可能扰乱产生此类肽段的加工过程。以破伤风毒素C片段蛋白作为测试案例，我们发现天冬酰胺残基的自发脱酰胺作用会干扰天冬酰胺内肽酶（AEP）的加工过程，并导致抗原呈递减少。当AEP靶向的天冬酰胺残基被修饰时，脱酰胺作用直接抑制AEP活性；当相邻的天冬酰胺残基脱酰胺时，则间接抑制AEP活性。因此，长寿自身蛋白质的脱酰胺作用可能在质量或数量上影响呈递给T细胞的自身肽段谱，从而可能促使自身免疫性疾病的发生或加剧。
