A role for intercellular antigen transfer in the recognition of EBV-transformed B cell lines by EBV nuclear antigen-specific CD4+ T cells

被引:57
作者
Taylor, Graham S. [1 ]
Long, Heather M. [1 ]
Haigh, Tracey A. [1 ]
Larsen, Martin [1 ]
Brooks, Jill [1 ]
Rickinson, Alan B. [1 ]
机构
[1] Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham B15 2TT, W Midlands, England
基金
英国医学研究理事会;
关键词
D O I
10.4049/jimmunol.177.6.3746
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The CD4(+) T cell response to EBV may have an important role in controlling virus-driven B lymphoproliferation because CD4(+) T cell clones to a subset of EBV nuclear Ag (EBNA) epitopes can directly recognize virus-trinsformed lymphoblastoid. cell lines (LCLs) in vitro and inhibit their growth. In this study, we used a panel of EBNA1, 2, 3A, and 3C-specific CD4(+) T cell clones to study the route whereby endogenously expressed EBNAs access the HLA class II-presentation pathway. Two sets of results spoke against a direct route of intracellular access. First, none of the clones recognized cognate Ag overexpressed in cells from vaccinia vectors but did recognize Ag fused to an endo/lysosomal targeting sequence. Second, focusing on clones with the strongest LCL recognition that were specific for EBNA2- and EBNA3C-derived epitopes LCL recognition was unaffected by inhibiting autophagy, a postulated route for intracellular Ag delivery into the HLA class II pathway in LCL cells. Subsequently, using these same epitope-specific clones, we found that Ag-negative cells with the appropriate HLA-restricting allele could be efficiently sensitized to CD4(+) T cell recognition by cocultivation with Ag-positive donor lines or by exposure to donor line-conditioned culture medium. Sensitization was mediated by a high m.w. antigenic species and required active Ag processing by recipient cells. We infer that intercellular Ag transfer plays a major role in the presentation of EBNA-derived CD4 epitopes by latently infected target cells.
引用
收藏
页码:3746 / 3756
页数:11
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