INVIVO COMPETITION BETWEEN SELF PEPTIDES AND FOREIGN ANTIGENS IN T-CELL ACTIVATION
INVIVO COMPETITION BETWEEN SELF PEPTIDES AND FOREIGN ANTIGENS IN T-CELL ACTIVATION
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DOI：
10.1038/334623a0
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发表时间：
1988-08-18
期刊：
影响因子：
64.8
通讯作者：
NAGY, ZA
中科院分区：
文献类型：
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作者：
ADORINI, L;MULLER, S;NAGY, ZA
细胞毒性T淋巴细胞和辅助性T淋巴细胞分别识别与I类和II类主要组织相容性复合体（MHC）分子相关的短肽形式的外源抗原1 -4。最近对I类MHC分子的三维结构的研究揭示了由蛋白质的氨基末端的一半形成的裂缝，其可以作为这些肽的结合位点5 -6。由于个体仅具有有限的一组不同的MHC分子，因此该组中的每个分子必须具有结合大量不同肽的能力，以确保完全的免疫活性。因此，可以预期，具有不相关序列的肽竞争与相同MHC分子的结合，并且，事实上，这已显示在体外发生7，8。因此，我们决定看看这种竞争是否也可以调节体内T细胞的反应。我们已经发现，对应于小鼠溶菌酶残基46-62的合成肽，虽然本身没有免疫原性，但当与外源蛋白或肽抗原一起注射到小鼠中时，有效地抑制T细胞应答的引发。观察到的抑制与竞争者结合呈递外源抗原的特定MHC分子的能力严格相关，其程度取决于抗原和竞争者之间的摩尔比。
Cytotoxic and helper T lymphocytes recognize foreign antigen in the form of short peptides associated with class I and class II major histocompatibility complex (MHC) molecules, respectively1–4. A recent study of the three-dimensional structure of a class I MHC molecule revealed a cleft formed by the amino-terminal half of the protein, which could serve as the binding site for these peptides5–6. Because an individual possesses only a limited set of different MHC molecules, each molecule of this set must have the ability to bind a large number of different peptides in order to ensure full immunocompetence. Thus, it can be anticipated that peptides with unrelated sequences compete for binding to the same MHC molecule, and, indeed, this has been shown to occurin vitro7,8. We therefore decided to see whether such competition could also regulate T-cell responsesin vivo. We have found that a synthetic peptide corresponding to residues 46–62 of mouse lysozyme, although not immunogenic itself, effectively inhibits the priming for T-cell responses when injected into mice together with foreign protein or peptide antigens. The inhibition observed strictly correlates with the capacity of the competitor to bind to the particular MHC molecule presenting the foreign antigen, and its extent depends on the molar ratio between antigen and competitor.