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Tissue specificity of cross-reactive allogeneic responses by EBV EBNA3A-specific memory T Cells

DʼOrsogna, L.J.A., Roelen, D.L., van der Meer-Prins, E.M.W., van der Pol, P., Franke-van Dijk, M.E., Eikmans, M., Anholts, J., Rossjohn, J., McCluskey, J., Mulder, A., van Kooten, C., Doxiadis, I.I.N. and Claas, F.H.J. (2011) Tissue specificity of cross-reactive allogeneic responses by EBV EBNA3A-specific memory T Cells. Transplantation, 91 (5). pp. 494-500.

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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*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*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*44:02 and HLA-B*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*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*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*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.

Item Type: Journal Article
Publisher: Wolters Kluwer Health
Copyright: © 2017 Wolters Kluwer Health
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