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Tissue specificity of cross-reactive allogeneic responses by EBV EBNA3A-specific memory T Cells
Journal article   Peer reviewed

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

L.J.A. DʼOrsogna, D.L. Roelen, E.M.W. van der Meer-Prins, P. van der Pol, M.E. Franke-van Dijk, M. Eikmans, J. Anholts, J. Rossjohn, J. McCluskey, A. Mulder, …
Transplantation, Vol.91(5), pp.494-500
2011
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Abstract

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.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.6 Immunology
1.6.127 T Cell Regulation
Web Of Science research areas
Immunology
Surgery
Transplantation
ESI research areas
Clinical Medicine
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