DIFFERENT MHC CLASS-I ALLELES COMPETE FOR PRESENTATION OF OVERLAPPING VIRAL EPITOPES

DIFFERENT MHC CLASS-I ALLELES COMPETE FOR PRESENTATION OF OVERLAPPING VIRAL EPITOPES
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DOI:
10.1016/1074-7613(95)90159-0
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发表时间:
1995-07-01
期刊:
影响因子:
32.4
通讯作者:
MCMICHAEL, AJ
MCMICHAEL, AJ
中科院分区:
医学1区
文献类型:
--
作者:
TUSSEY, LG;ROWLANDJONES, S;MCMICHAEL, AJ

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我们先前鉴定了HLA-B8(+)供体NW,其淋巴母细胞样细胞在病毒感染后未能呈递来自甲型流感核蛋白的B8限制性表位,尽管仍可以呈递添加的肽。病毒感染后不能通过HLA-88呈递似乎对NP表位具有特异性。在这里,我们报告说,捐助者NW使HLA-B2702限制性流感特异性CTL反应的核蛋白中的表位,重叠的B8限制性表位由8个氨基酸。两种机制的失败,这种细胞系提出的B8限制性表位病毒感染后进行了调查。一个是,存在特异于NW细胞系的抗原加工多态性,使得存在B2702表位的优先产生或优先转运。另一个是B8和B2702竞争ER中的共同肽片段,这导致HLA-B8的次优负载。
We previously identified an HLA-B8(+) donor, NW, whose lymphoblastoid cells failed to present a B8-restricted epitope from the influenza A nucleoprotein following viral infection, although added peptide could still be presented. The failure to present through HLA-88 following viral infection appears to be specific for the NP epitope. Here, we report that donor NW makes an HLA-B2702-restricted influenza-specific CTL response to an epitope in the nucleoprotein that overlaps the B8-restricted epitope by 8 aa. Two mechanisms for the failure of this cell line to present the B8-restricted epitope following viral infection are investigated. One is that there is an antigen processing polymorphism specific to the NW cell line, so that there is either preferential generation or preferential transport of the B2702 epitope. The other is that B8 and B2702 compete for a common peptide fragment in the ER and this leads to suboptimal loading of HLA-B8.