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Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine
Lichen Jing, … , Georges M.G.M. Verjans, David M. Koelle
Lichen Jing, … , Georges M.G.M. Verjans, David M. Koelle
Published January 3, 2012
Citation Information: J Clin Invest. 2012;122(2):654-673. https://doi.org/10.1172/JCI60556.
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Technical Advance Infectious disease Article has an altmetric score of 3

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

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Abstract

Herpes simplex virus type 1 (HSV-1) not only causes painful recurrent oral-labial infections, it can also cause permanent brain damage and blindness. There is currently no HSV-1 vaccine. An effective vaccine must stimulate coordinated T cell responses, but the large size of the genome and the low frequency of HSV-1–specific T cells have hampered the search for the most effective T cell antigens for inclusion in a candidate vaccine. We have now developed what we believe to be novel methods to efficiently generate a genome-wide map of the responsiveness of HSV-1–specific T cells, and demonstrate the applicability of these methods to a second complex microbe, vaccinia virus. We used cross-presentation and CD137 activation–based FACS to enrich for polyclonal CD8+ T effector T cells. The HSV-1 proteome was prepared in a flexible format for analyzing both CD8+ and CD4+ T cells from study participants. Scans with participant-specific panels of artificial APCs identified an oligospecific response in each individual. Parallel CD137-based CD4+ T cell research showed discrete oligospecific recognition of HSV-1 antigens. Unexpectedly, the two HSV-1 proteins not previously considered as vaccine candidates elicited both CD8+ and CD4+ T cell responses in most HSV-1–infected individuals. In this era of microbial genomics, our methods — also demonstrated in principle for vaccinia virus for both CD8+ and CD4+ T cells — should be broadly applicable to the selection of T cell antigens for inclusion in candidate vaccines for many pathogens.

Authors

Lichen Jing, Jürgen Haas, Tiana M. Chong, Joseph J. Bruckner, Greg C. Dann, Lichun Dong, Joshua O. Marshak, Christopher L. McClurkan, Tori N. Yamamoto, Susanne M. Bailer, Kerry J. Laing, Anna Wald, Georges M.G.M. Verjans, David M. Koelle

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Figure 10

Detection and enrichment of vaccinia-specific CD8+ and CD4+ T cells.

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Detection and enrichment of vaccinia-specific CD8+ and CD4+ T cells.
   ...
(A) Left panels show expression of CD137 after 20 hours of exposure of CD8+ T cells to cross-presented mock or vaccinia antigen. Small boxes indicate approximate gates for FACS. Numbers are percent of total gated live CD3+ lymphocytes in each quadrant. Right panels show IFN-γ expression by bulk, expanded CD8+ CD137hi or CD137lo cells in response to exposure to autologous B-LCLs in the absence or presence of vaccinia infection, or positive control stimulus. Numbers are percentages of gated live, CD3+ lymphocytes in each quadrant. (B) Cytolytic activity of bulk, expanded CD8+CD137hi cells to autologous or allogeneic APCs with or without vaccinia infection. (C) Left panels show expression of CD137 by CD4+ T cells after 20 hours of exposure of PBMCs to UV-inactivated, cell-associated mock or vaccinia antigen. Small boxes indicate approximate gates for FACS. Numbers are percentages of gated live, CD3+ lymphocytes in each quadrant. Right panels show IFN-γ and IL-2 expression of polyclonal expanded CD4+ CD137hi or CD137lo cells to autologous APCs and mock or vaccinia antigen. APCs were CFSE dump-gated. Numbers are percentages of live, CD4+ cells in each quadrant.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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