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The CD8 and CD4 T-Cell Response against Kaposi's Sarcoma-Associated Herpesvirus Is Skewed Towards Early and Late Lytic Antigens

Robey, RC; Lagos, D; Gratrix, F; Henderson, S; Matthews, NC; Vart, RJ; Bower, M; ... Gotch, FM; + view all (2009) The CD8 and CD4 T-Cell Response against Kaposi's Sarcoma-Associated Herpesvirus Is Skewed Towards Early and Late Lytic Antigens. PLOS ONE , 4 (6) , Article e5890. 10.1371/journal.pone.0005890. Green open access

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Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally related to Kaposi's sarcoma (KS), the most common malignancy in untreated individuals with HIV/AIDS. The adaptive T-cell immune response against KSHV has not been fully characterized. To achieve a better understanding of the antigenic repertoire of the CD8 and CD4 T-cell responses against KSHV, we constructed a library of lentiviral expression vectors each coding for one of 31 individual KSHV open reading frames (ORFs). We used these to transduce monocyte-derived dendritic cells (moDCs) isolated from 14 KSHV-seropositive (12 HIV-positive) and 7 KSHV-seronegative (4 HIV-positive) individuals. moDCs were transduced with up to 3 KSHV ORFs simultaneously (ORFs grouped according to their expression during the viral life cycle). Transduced moDCs naturally process the KSHV genes and present the resulting antigens in the context of MHC class I and II. Transduced moDCs were cultured with purified autologous T cells and the CD8 and CD4 T-cell proliferative responses to each KSHV ORF (or group) was assessed using a CFSE dye-based assay. Two pools of early lytic KSHV genes ([ORF8/ORF49/ORF61] and [ORF59/ORF65/K4.1]) were frequently-recognized targets of both CD8 and CD4 T cells from KSHV seropositive individuals. One pool of late lytic KSHV genes ([ORF28/ORF36/ORF37]) was a frequently-recognized CD8 target and another pool of late genes ([ORF33/K1/K8.1]) was a frequently-recognized CD4 target. We report that both the CD8 and CD4 T-cell responses against KSHV are skewed towards genes expressed in the early and late phases of the viral lytic cycle, and identify some previously unknown targets of these responses. This knowledge will be important to future immunological investigations into KSHV and may eventually lead to the development of better immunotherapies for KSHV-related diseases.

Type: Article
Title: The CD8 and CD4 T-Cell Response against Kaposi's Sarcoma-Associated Herpesvirus Is Skewed Towards Early and Late Lytic Antigens
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0005890
Publisher version: http://dx.doi.org/10.1371/journal.pone.0005890
Language: English
Additional information: © 2009 Robey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by grant G0800168 from the Medical Research Council (http://www.mrc.ac.uk) and grant JRC 08/09 SG 006 from the Westminster Medical School Research Trust and the Chelsea and Westminster Health Charity (http://www.chelwestcharity.org.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1299600
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