Study on the ability of dengue virus HLA-A*0201-restricted T-cell epitopes in inducing T cell response
DUAN Zhiliang1, LI Dezhou2, XU Juanjuan3, JIA Qingjun3, LIU Huifang3, CHEN Bokun3, WEN Jinsheng3
1.Department of Laboratory, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027; 2.Department of Liver, the Second Hospital of Ningbo, Ningbo, 315000; 3.Institute of Arboviruses, Wenzhou Medical University, Wenzhou, 325035
DUAN Zhiliang,LI Dezhou,XU Juanjuan, et al. Study on the ability of dengue virus HLA-A*0201-restricted T-cell epitopes in inducing T cell response[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2016, 46(6): 397-403.
Abstract：Objective: To explore the ability of dengue virus (DENV)-specific HLA-A*0201-restricted T cell-epitope to induce DENV serotype cross-reactive T cell response. Methods: Based on the sequence of one previously identified DENV-1-specific HLA-A*0201-restricted CD8+ T-cell epitope (NS4b40-48TLYAVATTI), the epitope variants in other DENV serotypes were synthesized and their binding affinity for HLA-A*0201 molecule was determined by using MHC-peptide complex stabilization assay. These peptides were used to immunize HLA-A*0201 transgenic mice, and the ability of induced CD8+ T cells to recognize the same epitope and epitope variant was evaluated by using enzyme-linked immunospot (ELISPOT) assay; Finally, individual DENV serotype was used to infect HLA-A*0201 transgenic mice and ELISPOT assay was utilized to assess whether the induced CD8+ T cells could recognize same epitope or epitope variant. Results: The epitope candidate in DENV-3 (NS4b39-47TLYAVATTV) had high affinity for HLA-A*0201 molecule while the epitope candidate in DENV-2 (NS4b39-47TLYAVATTF) bound to HLA-A*0201 molecule with a low affinity. Both DENV-1-NS4b40-48 and DENV-3-NS4b39-47 elicited DENV serotype cross-reactive CD8+ T cells which were distributed in the spleen, lymph nodes, peripheral blood of peptide-immunized transgenic mice and could recognize DENV-1-NS4b40-48, DENV-2-NS4b39-47 and DENV-3-NS4b39-47 simultaneously. Additionally, the same phenomenon was observed in DENV-1, -2, -3-infected HLA-A*0201 transgenic mice. Conclusion: DENV-3-derived NS4b39-47TLYAVATTV is identified as novel CD8+ T-cell epitope. Both this epitope and a previously identified epitope (NS4b40-48TLYAVATTI) triggered DENV serotype cross-reactive CD8+ T cell response, which would help us clarify the function of DENV serotype cross-reactive CD8+ T cells and evaluate the immunogenicity of DENV vaccine.
