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198 Development of HLA-B7 Supertype-Binding HIV Cytotoxic T Lymphocyte Vaccines
D. Berger, N. Bambard, and D. R. Lee*
Univ. of Missouri, Columbia, USA
The HLA-B7 supertype consists of 9 different class I alleles including the more prevalent HLA-B7 and -B35 alleles and the moderately prevalent HLA-B51, -B53, -B54, and -B55 alleles. Alleles within a particular supertype are predicted to be capable of binding peptide epitopes with similar anchor motifs. The ability of HIV cytotoxic T lymphocyte (CTL) epitopes to bind to multiple HLA alleles and induce protective immune responses in associations with those alleles would provide broader protection in the human population and would therefore be favored in vaccine approaches. Fourteen HIV CTL epitope peptides that were discovered in HIV-infected individuals and are restricted to one of the above HLA-B7 supertype alleles were chosen from the Los Alamos HIV CTL database for further study. These epitopes were examined for their ability to bind to the other above HLA-B7 supertype alleles using a cell-based binding assay. Interestingly, only the HLA-B55-restricted epitope, HIV gag215-223, was able to bind strongly to another HLA-B7 supertype allele, namely HLA-B7. Moreover, the HLA-B7/HIV gag215-223 complexes were comparatively long lived, suggesting that they might be immunogenic. To test the immunogenicity of the HLA-B55-restricted epitope in association with HLA-B7, dendritic cells from an HIV-uninfected, HLA-B7+ donor pulsed with either an HLA-B7-restricted HIV CTL epitope, nef72-80, or the HLA-B55-restricted HIV epitope were used to repeatedly stimulate autologous CD8+ T lymphocytes. After 2 such stimulations, the frequencies of responding cells were monitored, respectively, with either HLA-B7/HIV nef72-80 or HLA-B7/HIV gag215-223 tetramers. These preliminary results suggested that the HLA-B55-restricted peptide is immunogenic in association with HLA-B7, although less efficient than the HLA-B7-restricted HIV CTL epitope. These results provide support for the use of epitopes capable of binding to multiple HLA class I alleles to induce CTL responses in vaccine approaches.
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