Recycling MHC class I molecules and endosomal peptide loading
Recycling MHC class I molecules and endosomal peptide loading
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DOI：
10.1073/pnas.96.18.10326
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发表时间：
1999-08-31
影响因子：
11.1
通讯作者：
Neefjes, J
中科院分区：
文献类型：
--
作者：
Grommé, M;Uytdehaag, FGCM;Neefjes, J
MHC I类分子通常呈现由内源性抗原衍生的多肽，这些多肽结合在内质网中，外源抗原负载到I类分子上，例如在交叉启动中，但抗原片段和I类分子之间发生相互作用的细胞内位置尚不清楚。在这里，我们发现麻疹病毒F蛋白可以由第I类转运蛋白呈递，与抗原处理无关，对NH4Cl敏感，这表明第I类分子能够与酸性隔室中的抗原相互作用和结合，就像第II类分子一样。对活细胞内绿色荧光蛋白标记的I类分子的细胞内转运的研究证实，一小部分I类分子确实进入了经典的MNC：II类隔室(MIICs)，并在MIICs中被运输回质膜。分级研究表明，MIICs中的I类复合体含有多肽。MIIC的pH值在5.0左右，可以进行有效的多肽交换。因此，我们提出了与II类分子共享的I类负载途径的证据。
MHC class I molecules usually present peptides derived from endogenous antigens that are bound in the endoplasmic reticulum, Loading of exogenous antigens on class I molecules, e.g., in cross-priming, sometimes occurs, but the intracellular location where interaction between the antigenic fragment and class I takes place is unclear. Here we show that measles virus F protein can be presented by class I in transporters associated with antigen processing-independent, NH4Cl-sensitive manner, suggesting that class I molecules are able to interact and bind antigen in acidic compartments, like class II molecules. Studies on intracellular transport of green fluorescent protein-tagged class I molecules in living cells confirmed that a small fraction of class I molecules indeed enters classical MNC: class II compartments (MIICs) and is transported in MIICs back to the plasma membrane. Fractionation studies show that class I complexes in MIICs contain peptides. The pH in MIIC (around 5.0) is such that efficient peptide exchange can occur. We thus present evidence for a pathway fur class I loading that is shared with class II molecules.