Identification of murine poxvirus-specific CD8+ CTL epitopes with distinct functional profiles.
Murine T cell epitopes against vaccinia virus (VV) have not been characterized to date in part due to the large and complex genome of VV. We have identified and characterized two CD8+ T cell epitopes on the A47L (modified VV Ankara strain (MVA)-029) and J6R (MVA-043) proteins of VV that are Db and Kb restricted, respectively. Following i.p. immunization with VV New York City Board of Health (NYCBH) strain, MVA-029 peptide-stimulated splenocytes secreted IFN-gamma from 7 days to 7 mo postimmunization, and virus-stimulated effectors were also able to lyse MVA-029-pulsed target cells at the same time points. In contrast, MVA-043 peptide-stimulated splenocytes secreted very low levels of IFN-gamma only at day 7 but maintained the ability to lyse target cells up to 2 mo postimmunization. Both MVA-029 and MVA-043 peptide-stimulated lymph node cells degranulated similarly as assessed by Ag-induced CD107 expression. T cell responses to whole-virus stimulation remained robust and steady during the acute and memory T cell response to VV. Identification of T cell epitopes on VV will enable further studies to increase our understanding of the role of CD8+ T cells in VV infection and assist in the design of new protective strategies.
Mathew
Anuja
A
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA. anuja.mathew@umassmed.edu
Terajima
Masanori
M
West
Kim
K
Green
Sharone
S
Rothman
Alan L
AL
Ennis
Francis A
FA
Kennedy
Jeffrey S
JS
D000595:Amino Acid Sequence; D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000502:physiology*; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D014765:Viral Vaccines; D007371:Interferon-gamma