Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by HLA-A2 heavy chain modifications.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by HLA-A2 heavy chain modifications.

Int Immunol. 2000 Sep;12(9):1293-302. Unique Identifier : AIDSLINE MED/20425420
Dela Cruz CS; Tan R; Rowland-Jones SL; Barber BH; Department of Immunology and Institute of Medical Science,; University of Toronto, Medical Sciences Building, 1 King's; College Circle, Ontario M5S 1A8, Canada.

Abstract: 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.

Keywords: JOURNAL ARTICLE Animal Cell Line COS Cells Epitopes/IMMUNOLOGY Flow Cytometry Genetic Vectors Human HIV-1 Reverse Transcriptase/*IMMUNOLOGY HLA-A2 Antigen/ANALYSIS/*IMMUNOLOGY Signal Peptides/GENETICS Support, Non-U.S. Gov't T-Lymphocyte Subsets/IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY Transformation, Genetic

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