EBV latent membrane proteins (LMPs) 1 and 2 as immunotherapeutic targets : LMP-specific CD4+ cytotoxic T cell recognition of EBV-transformed B cell lines
The EBV-latent membrane proteins (LMPs) 1 and 2 are among only three viral proteins expressed in EBV-associated Hodgkin's lymphoma and nasopharyngeal carcinoma. Since these tumors are HLA class I and class II-positive, the LMPs could serve as both CD8+ and CD4+ T cell targets. In contrast to CD8 responses, very little is known about CD4 responses to LMPs. In this study, we describe CD4+ T cell clones defining four LMP1- and three LMP2-derived peptide epitopes and their restricting alleles. All clones produced Th1-like cytokines in response to peptide and most killed peptide-loaded target cells by perforin-mediated lysis. Although clones to different epitopes showed different functional avidities in peptide titration assays, avidity per se was a poor predictor of the ability to recognize naturally infected B lymphoblastoid cell lines (LCLs) expressing LMPs at physiologic levels. Some epitopes, particularly within LMP1, consistently mediated strong LCL recognition detectable in cytokine release, cytotoxicity, and outgrowth inhibition assays. Using cyclosporin A to selectively block cytokine release, we found that CD4+ T cell cytotoxicity is the key effector of LCL outgrowth control. We therefore infer that cytotoxic CD4+ T cells to a subset of LMP epitopes could have therapeutic potential against LMP-expressing tumors.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:180 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 180(2008), 3 vom: 01. Feb., Seite 1643-54 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Haigh, Tracey A [VerfasserIn] |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 17.03.2008 Date Revised 16.05.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM176989471 |
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| 100 | 1 | |a Haigh, Tracey A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a EBV latent membrane proteins (LMPs) 1 and 2 as immunotherapeutic targets |b LMP-specific CD4+ cytotoxic T cell recognition of EBV-transformed B cell lines |
| 264 | 1 | |c 2008 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 17.03.2008 | ||
| 500 | |a Date Revised 16.05.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The EBV-latent membrane proteins (LMPs) 1 and 2 are among only three viral proteins expressed in EBV-associated Hodgkin's lymphoma and nasopharyngeal carcinoma. Since these tumors are HLA class I and class II-positive, the LMPs could serve as both CD8+ and CD4+ T cell targets. In contrast to CD8 responses, very little is known about CD4 responses to LMPs. In this study, we describe CD4+ T cell clones defining four LMP1- and three LMP2-derived peptide epitopes and their restricting alleles. All clones produced Th1-like cytokines in response to peptide and most killed peptide-loaded target cells by perforin-mediated lysis. Although clones to different epitopes showed different functional avidities in peptide titration assays, avidity per se was a poor predictor of the ability to recognize naturally infected B lymphoblastoid cell lines (LCLs) expressing LMPs at physiologic levels. Some epitopes, particularly within LMP1, consistently mediated strong LCL recognition detectable in cytokine release, cytotoxicity, and outgrowth inhibition assays. Using cyclosporin A to selectively block cytokine release, we found that CD4+ T cell cytotoxicity is the key effector of LCL outgrowth control. We therefore infer that cytotoxic CD4+ T cells to a subset of LMP epitopes could have therapeutic potential against LMP-expressing tumors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a EBV-associated membrane antigen, Epstein-Barr virus |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Viral Matrix Proteins |2 NLM | |
| 700 | 1 | |a Lin, Xiaorong |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Hui, Edwin P |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Anthony T C |e verfasserin |4 aut | |
| 700 | 1 | |a Rickinson, Alan B |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Graham S |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:180 |g year:2008 |g number:3 |g day:01 |g month:02 |g pages:1643-54 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 180 |j 2008 |e 3 |b 01 |c 02 |h 1643-54 | ||