Protein structure shapes immunodominance in the CD4 T cell response to yellow fever vaccination
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Protein structure shapes immunodominance in the CD4 T cell response to yellow fever vaccination. / Koblischke, Maximilian; Mackroth, Maria S; Schwaiger, Julia; Fae, Ingrid; Fischer, Gottfried; Stiasny, Karin; Heinz, Franz X; Aberle, Judith H.
In: SCI REP-UK, Vol. 7, No. 1, 21.08.2017, p. 8907.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Protein structure shapes immunodominance in the CD4 T cell response to yellow fever vaccination
AU - Koblischke, Maximilian
AU - Mackroth, Maria S
AU - Schwaiger, Julia
AU - Fae, Ingrid
AU - Fischer, Gottfried
AU - Stiasny, Karin
AU - Heinz, Franz X
AU - Aberle, Judith H
PY - 2017/8/21
Y1 - 2017/8/21
N2 - The live attenuated yellow fever (YF) vaccine is a highly effective human vaccine and induces long-term protective neutralizing antibodies directed against the viral envelope protein E. The generation of such antibodies requires the help of CD4 T cells which recognize peptides derived from proteins in virus particles internalized and processed by E-specific B cells. The CD4 T helper cell response is restricted to few immunodominant epitopes, but the mechanisms of their selection are largely unknown. Here, we report that CD4 T cell responses elicited by the YF-17D vaccine are focused to hotspots of two helices of the viral capsid protein and to exposed strands and loops of E. We found that the locations of immunodominant epitopes within three-dimensional protein structures exhibit a high degree of overlap between YF virus and the structurally homologous flavivirus tick-borne encephalitis virus, although amino acid sequence identity of the epitope regions is only 15-45%. The restriction of epitopes to exposed E protein surfaces and their strikingly similar positioning within proteins of distantly related flaviviruses are consistent with a strong influence of protein structure that shapes CD4 T cell responses and provide leads for a rational design of immunogens for vaccination.
AB - The live attenuated yellow fever (YF) vaccine is a highly effective human vaccine and induces long-term protective neutralizing antibodies directed against the viral envelope protein E. The generation of such antibodies requires the help of CD4 T cells which recognize peptides derived from proteins in virus particles internalized and processed by E-specific B cells. The CD4 T helper cell response is restricted to few immunodominant epitopes, but the mechanisms of their selection are largely unknown. Here, we report that CD4 T cell responses elicited by the YF-17D vaccine are focused to hotspots of two helices of the viral capsid protein and to exposed strands and loops of E. We found that the locations of immunodominant epitopes within three-dimensional protein structures exhibit a high degree of overlap between YF virus and the structurally homologous flavivirus tick-borne encephalitis virus, although amino acid sequence identity of the epitope regions is only 15-45%. The restriction of epitopes to exposed E protein surfaces and their strikingly similar positioning within proteins of distantly related flaviviruses are consistent with a strong influence of protein structure that shapes CD4 T cell responses and provide leads for a rational design of immunogens for vaccination.
KW - Journal Article
U2 - 10.1038/s41598-017-09331-w
DO - 10.1038/s41598-017-09331-w
M3 - SCORING: Journal article
C2 - 28827760
VL - 7
SP - 8907
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -