A role for intercellular antigen transfer in the recognition of EBV-transformed B cell lines by EBV nuclear antigen-specific CD4+ T cells
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-transformed 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.
| Errataetall: |
CommentIn: Autophagy. 2007 Jan-Feb;3(1):60-2. - PMID 17102586 |
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| Medienart: |
Artikel |
| Erscheinungsjahr: |
2006 |
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| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:177 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 177(2006), 6 vom: 15. Sept., Seite 3746-56 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Taylor, Graham S [VerfasserIn] |
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| Themen: |
Antigens, Viral |
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| Anmerkungen: |
Date Completed 24.10.2006 Date Revised 15.08.2023 published: Print CommentIn: Autophagy. 2007 Jan-Feb;3(1):60-2. - PMID 17102586 Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM165168749 |
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| 245 | 1 | 2 | |a A role for intercellular antigen transfer in the recognition of EBV-transformed B cell lines by EBV nuclear antigen-specific CD4+ T cells |
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| 500 | |a Date Completed 24.10.2006 | ||
| 500 | |a Date Revised 15.08.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Autophagy. 2007 Jan-Feb;3(1):60-2. - PMID 17102586 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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-transformed 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antigens, Viral |2 NLM | |
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| 650 | 7 | |a Epstein-Barr Virus Nuclear Antigens |2 NLM | |
| 700 | 1 | |a Long, Heather M |e verfasserin |4 aut | |
| 700 | 1 | |a Haigh, Tracey A |e verfasserin |4 aut | |
| 700 | 1 | |a Larsen, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Brooks, Jill |e verfasserin |4 aut | |
| 700 | 1 | |a Rickinson, Alan B |e verfasserin |4 aut | |
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