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HTLV-1 gene expression by individual infected clones determines susceptibility to lysis by cytotoxic T lymphocytes specific for Tax and HBZ

Host cytotoxic T-lymphocyte (CTL) responses are critical in limiting expansion of HTLV-1-infected CD4+T-cells in vivo, and most individuals generate abundant Tax-specific CTL. Although Tax is immunodominant, the ability to efficiently present peptides from HBZ on MHC class 1 is associated with a lower proviral load and a reduced frequency of HAM/TSP. HBZ mRNA is expressed in vivo, directing proliferation of infected cells. However, HBZ-specific CTL were detectable in fresh PBMCs in only 25% of chronically infected individuals. We hypothesised that HBZ has evolved to evade the generation of effective HBZ-specific CTLs. To evaluate the selective capacity of a potent HBZ-specific CTL response, we assayed the ability of equally efficient Tax-and HBZ-specific CTL clones to kill unstimulated, naturally infected cells from 16 HLA-A*02+HTLV-1+ individuals. Infected cells which expressed Tax during the course of the assay upregulated surface expression of HLA-A*02, and were eliminated efficiently by Tax-specific CTL. HBZ-specific CTL killed Tax+ cells less efficiently, preferentially killing cells with high levels of HLA-A*02. As a proportion of infected cells do not express Tax owing to silencing, mutation or viral integration site (IS) location, we tested whether HBZ-specific CTLs could kill Tax- infected cells, using high-throughput sequencing to monitor survival of infected clones after CTL selection. We are now validating our findings using patient-derived HBZ-specific CTL, and mapping HBZ epitopes recognised in vivo. In conclusion, the efficacy of HBZ-specific CTLs appears to be limited by the level of antigen presentation, but may confer the ability to target infected cells which escape Tax-specific CTL.

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Correspondence to Aileen G Rowan.

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This article is published under license to BioMed Central Ltd. 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 work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Rowan, A.G., McCallin, A., Niederer, H.A. et al. HTLV-1 gene expression by individual infected clones determines susceptibility to lysis by cytotoxic T lymphocytes specific for Tax and HBZ. Retrovirology 11 (Suppl 1), O21 (2014).

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