Identification and analysis for cross-reactivity among hantaviruses of H-2b-restricted cytotoxic T-lymphocyte epitopes in Sin Nombre virus nucleocapsid protein.
Sin Nombre virus (SNV) causes hantavirus pulmonary syndrome (HPS), with a high rate of mortality in humans who are infected by the transmission of virus from the natural rodent host. In humans, cytotoxic T lymphocytes (CTL) specific for SNV appear to play an important role in the pathogenicity of HPS. There is a correlation between the frequencies of SNV-specific CTLs and the severity of HPS disease. In order to create a mouse model to study the role of SNV-specific T cells in vivo, T cell responses to SNV nucleocapsid (N) protein in B6.PL Thy1(a)/Cy mice (H-2(b)) immunized with plasmid DNA or recombinant vaccinia virus expressing SNV N protein were examined. Four peptides, NC94-101, NC175-189, NC217-231 and NC331-345, were recognized by CD8(+) T cells in CTL and ELISPOT assays in SNV N-immunized mice. Interestingly, two of these epitopes are located in the central region of the SNV N protein, where several human CD8(+) T-cell epitopes have been defined in Puumala virus and SNV. CTL lines specific for these four epitopes were cross-reactive to corresponding Puumala virus peptides, but only one of them was cross-reactive to Hantaan virus peptides. These results will enable the analysis of the roles of CTL in immunopathology of HPS in experimental mouse models of HPS.
Maeda
Ken
K
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
West
Kim
K
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Toyosaki-Maeda
Tomoko
T
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Rothman
Alan L
AL
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Ennis
Francis A
FA
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Terajima
Masanori
M
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D006476:Orthohantavirus / Q000276:immunology*; D018804:Hantavirus Pulmonary Syndrome / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D019251:Nucleocapsid / Q000276:immunology*; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D029261:Sin Nombre virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007519:Isoantigens; D019590:Nucleocapsid Proteins; D010446:Peptide Fragments