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.