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| IDENTIFICATION OF TARGET ANTIGENS FOR THE HUMAN CYTOTOXIC T-CELL RESPONSE TO EPSTEIN-BARR-VIRUS (EBV) - IMPLICATIONS FOR THE IMMUNE CONTROL OF EBV-POSITIVE MALIGNANCIES |
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| Author(s): MURRAY RJ, KURILLA MG, BROOKS JM, THOMAS WA, ROWE M, KIEFF E, RICKINSON AB |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 176 Issue: 1 Pages: 157-168 Published: JUL 1 1992 |
| Times Cited: 371 References: 53 |
| Abstract: Epstein-Barr virus (EBV), a human herpes virus with oncogenic potential, persists in B lymphoid tissues and is controlled by virus-specific cytotoxic T lymphocyte (CTL) surveillance. On reactivation in vitro, these CTLs recognize EBV-transformed lymphoblastoid cell lines (LCLs) in an HLA class I antigen-restricted fashion, but the viral antigens providing target epitopes for such recognition remain largely undefined. Here we have tested EBV-induced polyclonal CTL preparations from 16 virus-immune donors on appropriate fibroblast targets in which the eight EBV latent proteins normally found in LCLs (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, leader protein [LP], and latent membrane protein [LMP] 1 and 2) have been expressed individually from recombinant vaccinia virus vectors. Most donors gave multicomponent responses with two or more separate reactivities against different viral antigens. Although precise target antigen choice was clearly influenced by the donor's HLA class I type, a subset of latent proteins, namely EBNA 3A, 3B, and 3C, provided the dominant targets on a range of HLA backgrounds; thus, 15 of 16 donors gave CTL responses that contained reactivities to one or more proteins of this subset. Examples of responses to other latent proteins, namely LMP 2 and EBNA 2, were detected through specific HLA determinants, but we did not observe reactivities to EBNA 1, EBNA LP, or LMP 1. The bulk polyclonal CTL response in one donor, and components of that response in others, did not map to any of the known latent proteins, suggesting that other viral target antigens remain to be identified. This work has important implications for CTL control over EBV-positive malignancies where virus gene expression is often limited to specific subsets of latent proteins. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV BIRMINGHAM, DEPT CANC STUDIES, CANC RES CAMPAIGN LABS, BIRMINGHAM B15 2TJ, W MIDLANDS ENGLAND
2. HARVARD UNIV, DEPT MICROBIOL & MOLEC GENET, BOSTON, MA 02115 USA
3. HARVARD UNIV, DEPT MED, VIROL PROGRAM, BOSTON, MA 02115 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: JA759 |
| ISSN: 0022-1007 |
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