title: Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity.
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.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Honda
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Masaru
authors.initials: M
authors.lastname: Kanekiyo
authors.forename: Wataru
authors.initials: W
authors.lastname: Akahata
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kannan
authors.initials: K
authors.lastname: Natarajan
authors.forename: Howard
authors.initials: H
authors.lastname: Robinson
authors.forename: Tedi E
authors.initials: TE
authors.lastname: Asher
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: David H
authors.initials: DH
authors.lastname: Margulies
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006183:H-2 Antigens / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D015699:HIV Envelope Protein gp120; D064532:Histocompatibility Antigen H-2D