Tissue Specificity of Cross-Reactive Allogeneic Responses by EBV EBNA3A-Specific Memory T Cells
Tissue Specificity of Cross-Reactive Allogeneic Responses by EBV EBNA3A-Specific Memory T Cells
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DOI：
10.1097/tp.0b013e318207944c
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发表时间：
2011-03-15
期刊：
影响因子：
6.2
通讯作者：
Claas, Frans H. J.
中科院分区：
文献类型：
--
作者：
D'Orsogna, Lloyd J. A.;Roelen, Dave L.;Claas, Frans H. J.
背景资料。EB病毒(EB病毒)特异性CD8 T细胞与同种异体人类白细胞抗原B(STAR)44：02的交叉反应依赖于靶抗原递呈自身多肽EEYLQAFTY。在这项研究中，我们报告了同种异体人类白细胞抗原B(STAR)44：02(+)近端小管上皮细胞(PTECs)和人脐静脉内皮细胞(HUVECs)是EBV EBNA3A特异性T细胞的不良靶点。将Eey多肽外源负载到表达HUVECs和PTECs的HLAB(STAR)44：02和HLAB(STAR)44：03上。然后，将负载和卸载眼多肽的PTECs和HUVECs与我们的EBNA3A T细胞克隆的系列稀释液孵育，进行细胞毒性分析。尽管表达HLAB(STAR)44：02的PTECs被EBNA3AT细胞克隆根据效靶比特异性地裂解，但在没有多肽负载的情况下，外源性Eey多肽负载显著增加了裂解(15%vs.75%；P<；0.0001)。表达HL A-B(STAR)44：02的人脐静脉内皮细胞仅在外源性Eey多肽作用下裂解(0%vs.%；P<；0.0001)。排除了人类白细胞抗原表达缺失和ABCD3基因表达缺失是导致这些结果的原因。结论EBV EBNA3A T细胞克隆不能识别HLAB(STAR)44：02(+)上皮细胞和内皮细胞，是由于缺乏EEYLQAFTY多肽呈递所致。组织特异性(多肽依赖)同种异体反应性可能对移植监测和排斥反应有重要意义。
Background. The crossreactivity of Epstein-Barr virus (EBV Epstein-Barr virus nuclear antigen 3A [EBNA3A])-specific CD8 T cells against allogeneic human leukocyte antigen (HLA)-B(star)44:02 has been shown to be dependent on presentation of self-peptide EEYLQAFTY by the target antigen. In this study, we report that allogeneic HLA-B(star)44:02(+) proximal tubular epithelial cells (PTECs) and human umbilical vein endothelial cells (HUVECs) are poor targets for EBV EBNA3A-specific T cells.Methods. The EEY peptide was exogenously loaded onto HLA-B(star)44:02 and HLA-B(star)44:03-expressing PTECs and HUVECs. EEY-peptide-loaded, and unloaded, PTECs and HUVECs were then incubated with serial dilutions of our EBNA3A T-cell clone, in a cytotoxicity assay.Results. Although HLA-B(star)44:02-expressing PTECs were specifically lysed in proportion to the effector/target ratio by the EBNA3A T-cell clone, without peptide loading, lysis was greatly increased by exogenous EEY peptide loading (15% vs. 75%; P < 0.0001). HLA-B(star)44:02-expressing HUVECs were only lysed when loaded with exogenous EEY peptide (0% vs. 64%; P < 0.0001). Lack of HLA expression and lack of ABCD3 gene expression were excluded as a cause for these results. PTECs and HUVECs were specifically targeted by another alloreactive T-cell clone without exogenous peptide loading, suggesting that the lack of recognition of HLA-B(star)44:02(+) epithelial and endothelial cells by the EBV EBNA3A T-cell clone was due to lack of EEYLQAFTY peptide presentation.Conclusions. Tissue-specific (peptide dependent) alloreactivity may have important implications for transplantation monitoring and rejection.