Epitopes described in "Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity."

Article Authors:Mitsuo Honda; Rui Wang; Wing-Pui Kong; Masaru Kanekiyo; Wataru Akahata; Ling Xu; Kazuhiro Matsuo; Kannan Natarajan; Howard Robinson; Tedi E Asher; David A Price; Daniel C Douek; David H Margulies; Gary J Nabel
Article Title:Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity.
Reference Detail
Reference ID:1016406
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-2D(d) 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.
Affiliations:Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Reference Type:Literature
PubMed ID:19620307
Journal:J Immunol
Journal Volume:183
Article Pages:2425-34
Journal ISSN:0022-1767
Article Chemical List:AIDS Vaccines;Epitopes, T-Lymphocyte;H-2 Antigens;HIV Envelope Protein gp120;Histocompatibility Antigen H-2D
Article MeSH List:AIDS Vaccines(administration & dosage; genetics; immunology; metabolism); Animals; CD8-Positive T-Lymphocytes(immunology; metabolism; virology); Cell Line; Cells, Cultured; Clone Cells; Epitopes, T-Lymphocyte(administration & dosage; genetics; immunology; metabolism); Genetic Vectors(administration & dosage; immunology; metabolism); H-2 Antigens(administration & dosage; genetics; immunology; metabolism); HIV Envelope Protein gp120(administration & dosage; genetics; immunology; metabolism); Histocompatibility Antigen H-2D; Immunization, Secondary; Mice; Mice, Inbred BALB C; Protein Binding(genetics; immunology)
Curation Last Updated:2015-07-30 20:32:32