Braud V M, McMichael A J, Cerundolo V
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
Eur J Immunol. 1998 Feb;28(2):625-35. doi: 10.1002/(SICI)1521-4141(199802)28:02<625::AID-IMMU625>3.0.CO;2-I.
To investigate how early events in antigen processing affect the repertoire of peptides presented by MHC class I molecules, we compared the presentation of the influenza A nucleoprotein epitope 265-273 by HLA-A3 class I molecules in human and mouse cells. Mouse cells that express HLA-A3 failed to present the NP265-273 peptide when contained within the full-length nucleoprotein, to HLA-A3-restricted human cytotoxic T lymphocytes. However, when the epitope was generated directly in the cytosol using a recombinant vaccinia virus that expressed the nonamer peptide, mouse cells were recognized by HLA-A3-restricted CTL. Poor transport of the peptide by mouse TAP was not responsible for the defect as co-infection of mouse cells with recombinant vaccinia viruses encoding the full-length nucleoprotein and the human TAP1 and TAP2 peptide transporter complex failed to restore presentation. These results therefore demonstrate a differential processing of the influenza nucleoprotein in mouse and human cells. This polymorphism influences the repertoire of peptides presented by MHC class I molecules at the cell surface.
为了研究抗原加工早期事件如何影响MHC I类分子呈递的肽库，我们比较了人源和鼠源细胞中HLA - A3 I类分子对甲型流感病毒核蛋白表位265 - 273的呈递情况。表达HLA - A3的鼠源细胞在全长核蛋白中包含NP265 - 273肽时，无法将其呈递给受HLA - A3限制的人细胞毒性T淋巴细胞。然而，当使用表达九聚体肽的重组痘苗病毒在细胞质中直接产生该表位时，鼠源细胞能被受HLA - A3限制的CTL识别。小鼠TAP对肽的转运能力差并非导致该缺陷的原因，因为用编码全长核蛋白以及人TAP1和TAP2肽转运复合物的重组痘苗病毒共同感染鼠源细胞并不能恢复呈递。因此，这些结果证明了流感病毒核蛋白在小鼠和人细胞中的加工过程存在差异。这种多态性影响了细胞表面MHC I类分子呈递的肽库。
