Identification of immunogenic and cross-reactive chikungunya virus-specific CD4+ T cell epitopes in chronic chikungunya viral arthritic disease in humans 2271

Abstract Description Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic chikungunya virus disease (CHIKVD) marked by persistent debilitating arthralgia. At present, the exact cause of CHIKVD is not understood, and in humans, the targets of CD4+ T cells in CHIKV are currently unknown. Here, by stimulating peripheral blood mononuclear cells collected from patients suffering from chronic CHIKVD with peptides spanning the entire CHIKV genome, we provide a comprehensive landscape of CHIKV CD4+ T cell epitopes. We identified 123 novel CD4+ T cell epitopes and three immunodominant regions in E1, nsP1 and CP proteins. The immunodominance of these regions was mapped to optimal epitopes, characterized by the capacity to bind to many common HLA class II allelic variants. In addition, we designed and validated a new CHIKV-specific CD4+ T cell epitope megapool, spanning both structural and non-structural proteins, which can be a useful tool to study CHIKV-specific T cell responses in small blood volumes, typically available in pediatric samples. Finally, by in silico assessment of the conservation of the CHIKV proteome in a diverse set of alphaviruses, we defined CHIKV epitopes conserved across arthritogenic and encephalitic viruses. Overall, our work is the first to identify CD4+ T cell targets of CHIKV in humans, expanding our capacity to study the role of T cells in CHIKV pathogenesis and mapping targets of alphaviruses for vaccine design. Funding Sources Supported by NIH Contract Numbers 75N93019C00065 and 75N93024C00056 Topic Categories Viral Immunology (VIR)