pH dependence of MHC class I-restricted peptide presentation.
pH dependence of MHC class I-restricted peptide presentation.
复制标题
MHC I 类限制性肽呈递的 pH 依赖性。
作者：
A. Stryhn;L. Pedersen;T. Romme;A. C. Olsen;M. Nissen;C. Thorpe;S. Buus
MHC I类分子的功能是结合并将抗原肽呈递给细胞毒性T细胞。在这里，我们报告了i类限制性肽的呈现强烈依赖于pH。在酸性pH下，一些肽的呈现增强，而另一些肽的呈现则受到抑制。生化肽- mhc I类结合试验表明，肽- mhc I类复合物在中性pH下比在酸性pH下更稳定。我们认为，酸依赖性肽解离可以产生空的I类分子，并且由此产生的结合潜力可以被一部分肽- mhc I类组合利用，在某些情况下导致相当大的肽交换。我们进一步推测，肽类I配合物在酸性条件下的相对不稳定性可能会影响I类限制性银呈递的结果，因为不太稳定的相关肽可能在酸性反式高尔基网络通过时与I类分离，因此可能不会呈递。最后，我们的结果可能部分解释了内吞蛋白是如何通过MHC I类分子呈现给细胞毒性T细胞的。
The function of MHC class I molecules is to bind and present antigenic peptides to cytotoxic T cells. Here, we report that class I-restricted peptide presentation is strongly pH dependent. The presentation of some peptides was enhanced at acidic pH, whereas the presentation of others was inhibited. Biochemical peptide-MHC class I binding assays demonstrated that peptide-MHC class I complexes are more stable at neutral pH than at acidic pH. We suggest that acid-dependent peptide dissociation can generate empty class I molecules and that the resulting binding potential can be exploited by a subset of peptide-MHC class I combinations, in some cases leading to considerable peptide exchange. We further speculate that the relative instability of peptide-class I complexes under acidic conditions may affect the outcome of class I-restricted Ag presentation, as less stably associated peptides may dissociate from class I during passage of the acidic trans-Golgi network, and therefore may not be presented. Finally, our results may in part explain how endocytosed proteins can be presented by MHC class I molecules to cytotoxic T cells.