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感染细胞肽47(ICP47)的表达对抗原转运的抑制作用可阻止绒毛膜癌细胞系中HLA在细胞表面的表达。

Inhibition of antigen transport by expression of infected cell peptide 47 (ICP47) prevents cell surface expression of HLA in choriocarcinoma cell lines.

作者信息

Easterfield A J, Austen B M, Westwood O M

机构信息

Division of Immunology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK.

出版信息

J Reprod Immunol. 2001 Apr;50(1):19-40. doi: 10.1016/s0165-0378(00)00088-7.

Abstract

Cell surface expression of HLA class I (including non-classical HLA-G) in JEG3 (choriocarcinoma cell line) was blocked by stable transfection with the sequence encoding the Herpes simplex virus protein, infected cell peptide 47 (ICP47) inserted into a vector pCEP4. Intracellular expression of ICP47 protein in ICP47-transfected cells was demonstrated. The lack of HLA cell surface expression was likely to be due to blockage of peptide transport from the cytoplasm into the endoplasmic reticulum by ICP47. ICP47 is known to block the heterodimeric transporter associated with antigen processing (formed from TAP1 and TAP2). Western blotting with a polyclonal antibody to the C-terminus of TAP1 showed high expression of TAP1 in BeWo and JEG3, but not JAR cells, expression that was strongly upregulated by gamma-interferon. Gamma-interferon also upregulated the cell surface expression of HLA class I. TAP1 was strongly expressed in MC2 and MC3 extravillous cytotrophoblast cell lines immortalised with the SV40 large T antigen. The results suggest a role for non-classical HLA in the presentation of antigenic peptides to the immune system.

摘要

通过将编码插入载体pCEP4的单纯疱疹病毒蛋白感染细胞肽47(ICP47)的序列进行稳定转染,可阻断JEG3(绒毛膜癌细胞系)中HLA I类分子(包括非经典HLA - G)的细胞表面表达。已证实ICP47转染细胞中存在ICP47蛋白的细胞内表达。HLA细胞表面表达的缺失可能是由于ICP47阻断了肽从细胞质向内质网的转运。已知ICP47可阻断与抗原加工相关的异二聚体转运体(由TAP1和TAP2形成)。用针对TAP1 C末端的多克隆抗体进行的蛋白质印迹分析表明,TAP1在BeWo和JEG3细胞中高表达,但在JAR细胞中不表达,γ干扰素可强烈上调其表达。γ干扰素还上调了HLA I类分子的细胞表面表达。TAP1在经SV40大T抗原永生化的MC2和MC3绒毛外滋养层细胞系中强烈表达。结果表明非经典HLA在向免疫系统呈递抗原肽方面发挥作用。

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