the antiviral efficacy of hiv-specific cd8+ t-cells to a conserved epitope is heavily dependent on the infecting hiv-1 isolatehiv-specific cd8 + t细胞的抗病毒疗效守恒的抗原决定基是严重依赖于感染hiv - 1的分离.pdf

The Antiviral Efficacy of HIV-Specific CD8+ T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate 1¤ 2 2 2 1 Srinika R. F. Ranasinghe *, Holger B. Kramer , Cynthia Wright , Benedikt M. Kessler , Katalin di Gleria , 1,3 1 1 1 1 Yonghong Zhang , Geraldine M. Gillespie , Marie-Eve Blais , Abigail Culshaw , Tica Pichulik , Alison 1 1 1 1 Simmons , Sarah L. Rowland-Jones , Andrew J. McMichael , Tao Dong * 1 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom, 2 Henry Wellcome Building of Molecular Physiology, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom, 3 BeiJing You’An Hospital, BeiJing Capital University, BeiJing, China Abstract A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted Nef90–97 epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A–H) could activate antiviral activity in FL8-specific cytotoxic T- lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef