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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Immunology II Abstract 45
CD8+ T CELL RECOGNITION OF THE KSHV LATENT PROTEIN LANA1
Shereen Sabbah & Andrew D Hislop
CRUK Institute for Cancer Studies, The University of Birmingham, Edgbaston,
Birmingham, B15 2TT, UK
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) has been implicated in the development
of the endothelial malignancy, Kaposi’s sarcoma, and the B cell malignancies primary
effusion lymphoma and multicentric Castleman’s disease. In these malignancies as well
as KSHV infected cells, the viral genome maintenance protein latency associated nuclear
antigen 1 (LANA1) is expressed. Potentially then, LANA1 is an attractive immune target.
Similar to what is seen in the genome maintenance protein of the other human gammaherpesvirus,
Epstein-Barr virus EBNA1, LANA1 contains extensive amino acid repeat
sequences. In the case of EBNA1, these repeats reduce the efficiency of presentation of
EBNA1 derived epitopes to CD8+ T cells. To determine whether the repeats of LANA1
afford a similar protection, we established a model system to examine the ability of
CD8+ T cells to recognise target cells expressing either LANA1 or a LANA1 construct
deleted of the repeat region (LANA1-delta), both of which encode an inserted human
CD8+ T cell epitope. We find that cells expressing the LANA1-delta protein express
higher levels of this protein compared to the full length protein, yet CD8+ T cells
recognise both target cells types efficiently. In this model system then, the LANA1
repeat sequences give no protection against CD8+ T cell recognition. We are now
mapping CD8+ T cell epitopes contained in LANA1 and will establish CD8+ T cell clones
specific for identified epitopes. These T cell clones will be used to examine their ability to
recognise natively processed and presented LANA1 epitopes on KSHV-infected cells.
Presenting author Email: sxs463@bham.ac.uk
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