Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity.
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.
Honda
Mitsuo
M
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Wang
Rui
R
Kong
Wing-Pui
WP
Kanekiyo
Masaru
M
Akahata
Wataru
W
Xu
Ling
L
Matsuo
Kazuhiro
K
Natarajan
Kannan
K
Robinson
Howard
H
Asher
Tedi E
TE
Price
David A
DA
Douek
Daniel C
DC
Margulies
David H
DH
Nabel
Gary J
GJ
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
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D015699:HIV Envelope Protein gp120; D064532:Histocompatibility Antigen H-2D