Presentation of endogenous viral proteins in association with major histocompatibility complex class II: On the role of intracellular compartmentalization, invariant chain and the TAP transporter system
Presentation of endogenous viral proteins in association with major histocompatibility complex class II: On the role of intracellular compartmentalization, invariant chain and the TAP transporter system
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DOI：
10.1002/eji.1830251230
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发表时间：
1995-12-01
影响因子：
5.4
通讯作者：
Hengartner, H
中科院分区：
文献类型：
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作者：
Oxenius, A;Bachmann, MF;Hengartner, H
主要组织相容性复合体(MHC)II类相关抗原的提呈主要与细胞吞噬细胞摄取外源抗原有关，但也观察到内源性合成的抗原。我们研究了淋巴细胞性脉络膜脑膜炎病毒(LCMV)内源性合成的膜相关糖蛋白(GP)和胞浆核蛋白(NP)在小鼠专业抗原提呈细胞(APC)中的MHC II类相关递呈。由于LCMV是一种非细胞病变病毒，对细胞蛋白质合成的影响最小，因此它是一种方便的抗原提呈研究病毒。相比之下，大多数其他评估内源性合成病毒抗原的II类相关呈递的研究使用了牛痘、麻疹和流感病毒等溶细胞性病毒，这些病毒会严重干扰宿主细胞的功能。此外，大多数研究是使用非专业的APC进行的。我们发现内源性合成膜相关的LCMV-gp的II类相关递呈是有效的，并且不能被氯喹或亮肽素所抑制。与自述(TAP)系统相关的转运蛋白和不变链(II)都没有明显参与这一过程。相反，即使在II缺陷的APC中也没有观察到内源性合成的胞内LCMV-NP与MHC II类相关的呈现。因此，内源性合成的LCMV-gp的MHC II类负载显然不需要在氯喹和亮肽素不敏感的酸性内体隔室中处理。此外，尽管TAP分子运输长达15个氨基酸的多肽，这可能会与内质网中的MHC II类分子结合，但这种过程显然不会发生在糖蛋白或核蛋白中。因此，内源性合成蛋白的亚细胞定位对MHC II类负载是否能够独立于MHC II类负载中通常涉及的酸性隔室发生至关重要。
Major histocompatibility complex (MHC) class II-associated antigen presentation is mainly linked to processing of exogenous antigens upon cellular uptake by endocytosis, but has also been observed for endogenously sythesized antigens. We have studied the MHC class II-associated presentation of the endogenously synthesized membrane associated glycoprotein (GP) and the cytosolic nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) in professional antigen presenting cells (APC) of mice. Since LCMV is a noncytopathic virus and minimally affects cellular protein synthesis, it is a convenient virus for the study of antigen presentation. In contrast, most other studies assessing class II-associated presentation of endogeneously synthesized viral antigens used cytolytic viruses such as vaccinia, measles and influenza virus, which drastically interfere with host cell functions. In addition, most studies were performed using non-professional APC. We found that class II-associated presentation of endogenously synthesized membrane associated LCMV-GP was efficient and could not be inhibited by chloroquine or leupeptin. Neither the transporter associated with professing (TAP) system nor the invariant chain (Ii) were significantly involved in this process. In contrast, MHC class II-associated presentation of endogenously synthesized cytosolic LCMV-NP was not observed even in Ii-deficient APC. Thus, MHC class II loading of endogenously synthesized LCMV-GP apparently does not require processing in acidic endosomal compartments as defined by chloroquine and leupeptin insensitivity Furthermore, although the TAP molecules transport peptides of up to 15 amino acids in length, which potentially could bind to MHC class II molecules in the endoplasmic reticulum, such a process apparently does not occur for either the glycoprotein or the nucleoprotein. Therefore, the subcellular localization of an endogenously synthesized protein influences crucially whether or not MHC class II loading can occur independently of the acidic compartments usually involved in MHC class II loading.