Sequence evolution and escape from specific immune pressure of an HIV-1 Rev epitope with extensive sequence similarity to human nucleolar protein 6

Antigen‐specific immunity is crucially important for containing viral replication in human immunodeficiency virus (HIV)‐1‐infected hosts. Several epitopes have been predicted for the early expressed HIV‐1 proteins Tat and Rev, but few have been studied in detail. We characterized the human leukocyte antigen (HLA)‐B44‐restricted Rev epitope EELLKTVRL (EL9) in an HIV‐1‐infected subject treated with antiretroviral therapy. Interestingly, a high sequence similarity was found between the EL9 epitope and the human nucleolar protein 6 (NOL6). However, this similarity does not seem to impede immunogenicity as CD8+ T‐cells, previously stimulated with EL9‐pulsed dendritic cells, were able to specifically recognize the HIV‐1 Rev epitope without cross‐recognizing the human self‐antigen NOL6. After the subject interrupted antiretroviral therapy and virus rebounded, mutations within the EL9 epitope were identified. Although the emerging mutations resulted in decreased or abolished T‐cell recognition, they did not impair Rev protein function. Mutations leading to escape from T‐cell recognition persisted for up to 124 weeks following treatment interruption. This study shows that the HLA‐B44‐restricted Rev CD8+ T‐cell epitope EL9 is immunogenic notwithstanding its close resemblance to a human peptide. The epitope mutates as a consequence of dynamic interaction between T‐cells and HIV‐1. Clinical status, CD4+ T‐cell count and viral load remained stable despite escape from T‐cell recognition.