Human memory cytotoxic T-lymphocyte (CTL) responses to Hantaan virus infection: identification of virus-specific and cross-reactive CD8(+) CTL epitopes on nucleocapsid protein
Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research; Program in Immunology/Virology
Medical Subject Headings
Amino Acid Sequence; CD8-Positive T-Lymphocytes; Capsid; *Capsid Proteins; Cell Line; Cells, Cultured; Cross Reactions; Epitopes, T-Lymphocyte; HLA-A Antigens; HLA-B Antigens; Hantaan virus; Hemorrhagic Fever with Renal Syndrome; Humans; Immunologic Memory; Leukocytes, Mononuclear; Molecular Sequence Data; Peptides; T-Lymphocytes, Cytotoxic; Viral Core Proteins
Life Sciences | Medicine and Health Sciences
Hantaan virus, the prototypic member of the Hantavirus genus, causes hemorrhagic fever with renal syndrome in humans. We examined the human memory T-lymphocyte responses of three donors who had previous laboratory-acquired infections with Hantaan virus. We demonstrated virus-specific responses in bulk cultures of peripheral blood mononuclear cells (PBMC) from all donors. Bulk T-cell responses were directed against either Hantaan virus nucleocapsid (N) or G1 protein, and these responses varied between donors. We established both CD4(+) and CD8(+) N-specific cell lines from two donors and CD4(+) G1-specific cell lines from a third donor. All CD8(+) cytotoxic T-lymphocyte (CTL) lines recognized one of two epitopes on the nucleocapsid protein: one epitope spanning amino acids 12 to 20 and the other spanning amino acids 421 to 429. The CTL lines specific for amino acids 12 to 20 were restricted by HLA B51, and those specific for amino acids 421 to 429 were restricted by HLA A1. The N-specific CTL lines isolated from these two donors included both Hantaan virus-specific CTLs and hantavirus cross-reactive CTLs. Responses to both epitopes are detectable in short-term bulk cultures of PBMC from one donor, and precursor frequency analysis confirms that CTLs specific for these epitopes are present at relatively high precursor frequencies in the peripheral T-cell pool. These data suggest that infection with Hantaan virus results in the generation of CTL to limited epitopes on the nucleocapsid protein and that infection also results in the generation of cross-reactive T-cell responses to distantly related hantaviruses which cause the distinct hantavirus pulmonary syndrome. This is the first demonstration of human T-lymphocyte responses to Hantaan virus.
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Citation: J Virol. 1999 Jul;73(7):5301-8.
Journal of virology
Van Epps, Heather Lin; Schmaljohn, Connie S.; and Ennis, Francis A., "Human memory cytotoxic T-lymphocyte (CTL) responses to Hantaan virus infection: identification of virus-specific and cross-reactive CD8(+) CTL epitopes on nucleocapsid protein" (1999). GSBS Student Publications. 1282.