Different Vaccine Vectors Delivering the Same Antigen Elicit CD8+ T Cell Responses with Distinct Clonotype and Epitope Specificity
Open Access
- 15 August 2009
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 183 (4), 2425-2434
- https://doi.org/10.4049/jimmunol.0900581
Abstract
Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8+ cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8+ T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2Dd better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8+ T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.Keywords
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