MacAry P A, Lindsay M, Scott M A, Craig J I, Luzio J P, Lehner P J
Division of Immunology, Department of Pathology, Wellcome Trust Center for Molecular Mechanisms in Disease, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3982-7. doi: 10.1073/pnas.071477498.
Langerhans cells are a subset of dendritic cells (DCs) found in the human epidermis with unique morphological and molecular properties that enable their function as "sentinels" of the immune system. DCs are pivotal in the initiation and regulation of primary MHC class I restricted T lymphocyte immune responses and are able to present both endogenous and exogenous antigen onto class I molecules. Here, we study the MHC class I presentation pathway following activation of immature, CD34-derived human Langerhans cells by lipopolysaccharide (LPS). LPS induces an increase in all components of the MHC class I pathway including the transporter for antigen presentation (TAP), tapasin and ERp57, and the immunoproteasome subunits LMP2 and LMP7. Moreover, in CD34-derived Langerhans cells, the rapid increase in expression of MHC class I molecules seen at the cell surface following LPS activation is because of mobilization of MHC class I molecules from HLA-DM positive endosomal compartments, a pathway not seen in monocyte-derived DCs. Mobilization of class I from this compartment is primaquine sensitive and brefeldin A insensitive. These data demonstrate the regulation of the class I pathway in concert with the maturation of the CD34-derived Langerhans cells and suggest potential sites for antigen loading of class I proteins.
朗格汉斯细胞是人类表皮中发现的树突状细胞（DC）的一个亚群，具有独特的形态和分子特性，使其能够作为免疫系统的“哨兵”发挥作用。DC在主要组织相容性复合体（MHC）I类限制性T淋巴细胞免疫反应的启动和调节中起关键作用，并且能够将内源性和外源性抗原呈递到I类分子上。在此，我们研究了脂多糖（LPS）激活未成熟的、源自CD34的人类朗格汉斯细胞后MHC I类呈递途径。LPS诱导MHC I类途径的所有成分增加，包括抗原呈递转运体（TAP）、TAP结合蛋白和内质网蛋白57，以及免疫蛋白酶体亚基LMP2和LMP7。此外，在源自CD34的朗格汉斯细胞中，LPS激活后在细胞表面看到的MHC I类分子表达的快速增加是由于MHC I类分子从HLA-DM阳性内体区室的动员，这是单核细胞衍生的DC中未见的一条途径。从这个区室动员I类分子对伯氨喹敏感，对布雷菲德菌素A不敏感。这些数据证明了I类途径与源自CD34的朗格汉斯细胞成熟的协同调节，并提示了I类蛋白抗原加载的潜在位点。
