PMID- 21242884 OWN - NLM STAT- MEDLINE DCOM- 20110414 LR - 20171213 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 91 IP - 5 DP - 2011 Mar 15 TI - Tissue specificity of cross-reactive allogeneic responses by EBV EBNA3A-specific memory T cells. PG - 494-500 LID - 10.1097/TP.0b013e318207944c [doi] AB - 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. FAU - D'Orsogna, Lloyd J A AU - D'Orsogna LJ AD - Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands. l.j.a.d_orsogna@lumc.nl FAU - Roelen, Dave L AU - Roelen DL FAU - van der Meer-Prins, Ellen M W AU - van der Meer-Prins EM FAU - van der Pol, Pieter AU - van der Pol P FAU - Franke-van Dijk, Marry E AU - Franke-van Dijk ME FAU - Eikmans, Michael AU - Eikmans M FAU - Anholts, Jacqy AU - Anholts J FAU - Rossjohn, Jamie AU - Rossjohn J FAU - McCluskey, James AU - McCluskey J FAU - Mulder, Arend AU - Mulder A FAU - van Kooten, Cees AU - van Kooten C FAU - Doxiadis, Ilias I N AU - Doxiadis II FAU - Claas, Frans H J AU - Claas FH LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (ABCD3 protein, human) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (EBNA-3A antigen) RN - 0 (Epstein-Barr Virus Nuclear Antigens) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B44 Antigen) RN - 0 (Peptides) SB - IM MH - ATP-Binding Cassette Transporters/metabolism MH - CD8-Positive T-Lymphocytes/cytology/*immunology MH - Cells, Cultured MH - Cross Reactions/immunology MH - Endothelium, Vascular/cytology/immunology MH - Epstein-Barr Virus Nuclear Antigens/*immunology MH - HLA-B Antigens/metabolism MH - HLA-B44 Antigen MH - Herpesvirus 4, Human/*immunology MH - Humans MH - Kidney Tubules, Proximal/cytology/immunology MH - Organ Specificity/immunology MH - Peptides/metabolism EDAT- 2011/01/19 06:00 MHDA- 2011/04/16 06:00 CRDT- 2011/01/19 06:00 PHST- 2011/01/19 06:00 [entrez] PHST- 2011/01/19 06:00 [pubmed] PHST- 2011/04/16 06:00 [medline] AID - 10.1097/TP.0b013e318207944c [doi] PST - ppublish SO - Transplantation. 2011 Mar 15;91(5):494-500. doi: 10.1097/TP.0b013e318207944c.