Identification and Characteristics of HLA-restricted HMPV-specific CD8+ T cells

Abstract

Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in pediatric, elderly, and immunocompromised populations. All individuals have been exposed to HMPV by the age of 5, but humoral immunity does not fully protect against reinfection of adults. Despite the clinical burden, there are currently no FDA-approved vaccines or therapeutics for HMPV. T cell responses are important for protection and viral clearance. The aim of this study was to better understand the human T cell response to HMPV and guide vaccine development. To accomplish these goals, we sought to identify HLA class I-restricted viral epitopes. In this study, 5 transgenic mouse strains that express human HLA-A*01:03, HLA-A*24:01, HLA-B*35:01, HLA-B*15:02, or HLA-Cw*07:01 were used to map HMPV-specific epitopes and characterize HMPV-specific CD8+ T cells. We used ELISpot screening of overlapping peptides and predictopes to discover several epitopes and generate MHC-I tetramers for each genetic background. We found that human CD8+ T cells of subjects expressing the same HLA types could recognize viral epitopes by ELISpot and tetramer staining. Our results suggest that the transgenic mouse is a useful model to identify HLA-restricted viral-specific epitopes and novel targets for vaccination against HMPV. Supported by grants from NIH (R01 AI085062)