IRREVERSIBLE ASSOCIATION OF PEPTIDES WITH CLASS-II MHC MOLECULES IN LIVING CELLS
IRREVERSIBLE ASSOCIATION OF PEPTIDES WITH CLASS-II MHC MOLECULES IN LIVING CELLS
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DOI：
10.1038/357249a0
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发表时间：
1992-05-21
期刊：
影响因子：
64.8
通讯作者：
WATTS, C
中科院分区：
文献类型：
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作者：
LANZAVECCHIA, A;REID, PA;WATTS, C
功能、形态学和生物化学证据表明，II类主要组织相容性复合体（MHC）分子在生物合成1-9期间与加工肽相关。据报道，活细胞中的肽/MHC复合物比体外产生的类似复合物更不稳定，这导致了可能存在在体内起作用的肽交换机制的建议10-12。虽然这可以增加结合进入的抗原的能力，但它会通过将这些抗原肽交换为自身肽而降低加工的抗原肽的功效。在这里，我们测量了人类抗原呈递细胞中肽/II类复合物的半衰期，发现它与II类分子本身的半衰期非常相似，这表明肽在生理条件下是不可逆结合的。因此，II类MHC保留了过去与抗原接触的长期“记忆”，以最大化T细胞/抗原呈递细胞相互作用的机会。
FUNCTIONAL, morphological and biochemical evidence indicates that class II major histocompatibility complex (MHC) molecules associate with processed peptides during biosynthesis 1-9. Peptide/MHC complexes in living cells have been reported to be less stable than similar complexes generated in vitro, which has led to the suggestion that there may be a peptide exchange mechanism operating in vivo 10-12. Although this could increase the capacity for binding incoming antigens, it would reduce the efficacy of processed antigenic peptides by exchanging these for self peptides. Here we measure the half-life of peptide/class II complexes in human antigen-presenting cells and find that it is very similar to the half-life of class II molecules themselves, indicating that peptides are bound irreversibly under physiological conditions. Thus class II MHC retains long-term 'memory' of past encounters with antigen to maximize the opportunity for T cell/antigen-presenting cell interaction.