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PDBsum entry 3e6h
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Immune system
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PDB id
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3e6h
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References listed in PDB file
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Key reference
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Title
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Different vaccine vectors delivering the same antigen elicit cd8+ t cell responses with distinct clonotype and epitope specificity.
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Authors
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M.Honda,
R.Wang,
W.P.Kong,
M.Kanekiyo,
W.Akahata,
L.Xu,
K.Matsuo,
K.Natarajan,
H.Robinson,
T.E.Asher,
D.A.Price,
D.C.Douek,
D.H.Margulies,
G.J.Nabel.
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Ref.
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J Immunol, 2009,
183,
2425-2434.
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PubMed id
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Abstract
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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.
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