Presentation of an exogenous antigen by major histocompatibility complex class I molecules
Presentation of an exogenous antigen by major histocompatibility complex class I molecules
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主要组织相容性复合物 I 类分子呈递外源抗原
DOI：
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发表时间：
1994
影响因子：
5.4
通讯作者：
Margaret A. Liu
中科院分区：
文献类型：
--
作者：
J. Ulmer;J. Donnelly;Margaret A. Liu
细胞毒性T淋巴细胞（CTL）通常识别来自与新生的主要组织相容性复合体（MHC）I类分子相关的内源性表达蛋白的肽。相比之下，来自外源蛋白的肽在内吞作用至内体区室后与MHC II类结合。然而，我们最近已经证明，由假单胞菌外毒素（PE）的结合和易位结构域与衍生自流感基质蛋白（PEMa）或核蛋白的CTL表位融合组成的外源融合蛋白被I类MHC内化、加工、靶向并呈递（Donnelly等人，1993，Proc.Natl.Acad.Sci. Acad. Sci. USA 1993. 90：3530）。已知PE在细胞中毒期间被内化、在核内体中加工并易位至胞质溶胶。然而，我们目前的研究表明，与PE不同，PEMa不需要易位到胞质溶胶发挥其作用。首先，两种PE毒性抑制剂在内体加工后的步骤中发挥作用，对靶细胞对PEMa诱导的CTL介导的裂解的致敏作用没有影响。NH 4Cl通过升高内体pH抑制PE，布雷菲德菌素A通过破坏高尔基体复合体抑制PE，并不抑制PEMa对靶细胞的致敏作用。其次，PEMa能够对裂解T2突变细胞致敏，T2突变细胞在将肽从胞质溶胶转运到内质网腔以通过MHC I类呈递方面存在缺陷。这些结果表明，PEMa是在内涵体蛋白水解加工，并与MHC I类不需要新生的MHC分子。这样的过程可能涉及内化的MHC I类，随后在细胞表面上表达肽-MHC复合物，然后导致CTL识别。
Cytotoxic T lymphocytes (CTL) generally recognize peptides derived from endogenously expressed proteins in association with nascent major histocompatibility complex (MHC) class I molecules. In contrast, peptides derived from exogenous proteins associate with MHC class II following endocytosis to an endosomal compartment. However, we have recently demonstrated that exogenous fusion proteins consisting of the binding and translocating domains of Pseudomonas exotoxin (PE) fused with CTL epitopes derived from either influenza matrix protein (PEMa) or nucleoprotein are internalized, processed, targeted to and presented by MHC class I (Donnelly et al. 1993, Proc. Natl. Acad. Sci. USA 1993. 90: 3530). PE is known to be internalized, processed in endosomes, and translocated to the cytosol during intoxication of cells. However, our present studies demonstrate that, unlike PE, PEMa does not require translocation to the cytosol to exert its effect. First, two inhibitors of PE toxicity that exert their effects at steps subsequent to endosomal processing had no effect on the sensitization of target cells for CTL‐mediated lysis by PEMa. NH4Cl, which inhibits PE by raising endosomal pH, and brefeldin A, which inhibits PE by disrupting the Golgi complex, did not inhibit sensitization of targets cells by PEMa. Second, PEMa was capable of sensitizing for lysis T2 mutant cells, which are defective in transport of peptides from the cytosol to the lumen of the endoplasmic reticulum for presentation by MHC class I. These results suggest that PEMa is proteolytically processed in endosomes, and association with MHC class I does not require nascent MHC molecules. Such a process may involve internalized MHC class I, and subsequent expression of the peptide‐MHC complexes on the cell surface would then lead to recognition by CTL.
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I 类组织相容性分子的细胞内转运。
DOI：
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发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Williams,DB;Borriello,F;Zeff,RA;Nathenson,SG
通讯作者：
Nathenson,SG
DOI：
10.1016/s0021-9258(18)42291-0
发表时间：
1992-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Kounnas;Randal E. Morris;M. Thompson;Desmond J. Fitzgerald;D. Strickland;C. Saelinger
通讯作者：
M. Kounnas;Randal E. Morris;M. Thompson;Desmond J. Fitzgerald;D. Strickland;C. Saelinger
Brefeldin A 对小鼠红白血病细胞高尔基复合体、内质网和病毒包膜糖蛋白的影响。
影响因子：
6.6
作者：
Ulmer,JB;Palade,GE
通讯作者：
Palade,GE
影响因子：
3.7
作者：
T. Yoshida;C. Chen;M. Zhang;H. C. Wu
通讯作者：
T. Yoshida;C. Chen;M. Zhang;H. C. Wu
抗病毒细胞毒性 T 淋巴细胞诱导和疫苗接种。
DOI：
10.1093/clinids/10.1.16
发表时间：
1988
期刊：
Reviews of infectious diseases
影响因子：
--
作者：
Rouse,BT;Norley,S;Martin,S
通讯作者：
Martin,S