T cell epitopes were identified in HTNV structural protein (105.9)

Abstract

Abstract Objectives: To investigate the cellular immune response to Hantaan virus (HTNV) infection by identifying T cell epitopes of HTNV structural protein (nucleoprotein, NP and glycoprotein, Gn/Gc) and their HLA-restriction. Methods: The HLA-restriction of HTNV-NP T cell epitopes were identified by determining T cell response to peptide-loaded B lymphoblastoid cell lines which were HLA partially matched. T cell responses to an array of overlapping peptides derived from HTNV-Gn/Gc was quantitated by ex vivo IFN-γ ELISPOT analysis. Results: In the HTNV-NP, one HLA-A*02-, one HLA-B*07-, one HLA-A*11-, two HLA-A*33-, and three HLA-B*35-restricted T cell epitopes were identified. 86.6% hemorrhagic fever with renal syndrome (HFRS) patients (71/82) showed T cell response to 61.9% HTNV-Gn/Gc 15-mer peptides (174/281), in which, 11 potential dominant epitopes were screened out. Moreover, the response frequencies of HTNV-Gn/Gc-specific T cells at the earliest available time point were significantly higher in patients who had mild or moderate HFRS than in those who had severe or critical HFRS (P=0.007), suggesting that T cell response to these epitopes may affect HFRS disease progression in patients. Conclusion: T cell immunty plays a role in immunoprotection upon HTNV infection. Identification of T cell epitopes of HTNV structural protein and their HLA restriction may advance our understanding of immunoprotection and/or pathogenesis of HFRS, thereby improve the design of novel HTNV vaccine.