10.3389/fimmu.2018.02225.s001 Mei Qiu Lim Mei Qiu Lim Emmanuelle A. P. Kumaran Emmanuelle A. P. Kumaran Hwee Cheng Tan Hwee Cheng Tan David C. Lye David C. Lye Yee Sin Leo Yee Sin Leo Eng Eong Ooi Eng Eong Ooi Paul A. MacAry Paul A. MacAry Antonio Bertoletti Antonio Bertoletti Laura Rivino Laura Rivino Data_Sheet_1_Cross-Reactivity and Anti-viral Function of Dengue Capsid and NS3-Specific Memory T Cells Toward Zika Virus.PDF Frontiers 2018 dengue virus (DENV) Zika virus (ZIKV) T cells cross-reactive immune response heterologous immunity anti-viral response 2018-10-01 13:53:59 Dataset https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Cross-Reactivity_and_Anti-viral_Function_of_Dengue_Capsid_and_NS3-Specific_Memory_T_Cells_Toward_Zika_Virus_PDF/7152260 <p>Zika virus (ZIKV), a flavivirus with homology to dengue virus (DENV), is spreading to areas of DENV hyper-endemicity. Heterologous T cell immunity, whereby virus-specific memory T cells are activated by variant peptides derived from a different virus, can lead to enhanced viral clearance or diminished protective immunity and altered immunopathology. In mice, CD8+ T cells specific for DENV provide in vivo protective efficacy against subsequent ZIKV infection. In humans, contrasting studies report complete absence or varying degrees of DENV/ZIKV T cell cross-reactivity. Moreover, the impact of cross-reactive T cell recognition on the anti-viral capacity of T cells remains unclear. Here, we show that DENV-specific memory T cells display robust cross-reactive recognition of ZIKV NS3 ex vivo and after in vitro expansion in respectively n = 7/10 and n = 9/9 dengue-immune individuals tested. In contrast, cross-reactivity toward ZIKV capsid is low or absent. Cross-reactive recognition of DENV or ZIKV NS3 peptides elicits similar production of the anti-viral effector mediators IFN-γ, TNF-α, and CD107a. We identify 9 DENV/ZIKV cross-reactive epitopes, 7 of which are CD4+ and 2 are CD8+ T cell epitopes. We also show that cross-reactive CD4+ and CD8+ T cells targeting novel NS3 epitopes display anti-viral effector potential toward ZIKV-infected cells, with CD8+ T cells mediating direct lyses of these cells. Our results demonstrate that DENV NS3-specific memory T cells display anti-viral effector capacity toward ZIKV, suggesting a potential beneficial effect in humans of pre-existing T cell immunity to DENV upon ZIKV infection.</p>