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Vigorous HIV-1-specific CD8(+) cytotoxic T lymphocyte (CTL) responses play an important role in the control of HIV-1 replication and the induction of a strong, broadly cross-reactive CTL response remains an important goal of HIV vaccine development. It is known that the display of high levels of class I MHC-viral peptide complexes at the cell surface of target cells is necessary to elicit a strong CTL response. We now report two strategies to enhance the presentation of defined HIV-1 epitope-specific CTL target structures, by incorporating subdominant HIV-1 reverse transcriptase (RT) CTL epitope sequences into the human class I MHC molecule HLA-A2. We show that either incorporation of HIV-1 CTL epitopes into the signal sequence of HLA or tethering of epitopes to the HLA-A2 heavy chain provide simple ways to create effective CTL target structures that can be recognized and lysed by human HLA-A2-restricted RT-specific CD8(+) CTL. Moreover, cells expressing these epitope-containing HLA-A2 constructs stimulated the generation of primary epitope-specific CTL in vitro. These strategies offer new options in the design of plasmid DNA-based vaccines or immunotherapeutics for the induction of CTL responses against subdominant HIV-1 epitopes.

Original publication

DOI

10.1093/intimm/12.9.1293

Type

Journal article

Journal

Int Immunol

Publication Date

09/2000

Volume

12

Pages

1293 - 1302

Keywords

Animals, COS Cells, Cell Line, Epitopes, Flow Cytometry, Genetic Vectors, HIV Reverse Transcriptase, HLA-A2 Antigen, Humans, Protein Sorting Signals, T-Lymphocyte Subsets, T-Lymphocytes, Cytotoxic, Transformation, Genetic