title: Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.
abstract: Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in vaccinia and variola viruses. The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-gamma-producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-gamma-producing cells in one donor, 35% in the second donor, and 6% in the third donor. This information will be useful for studies of human T cell memory and for the design and analyses of the immunogenicity of experimental vaccinia vaccines.
authors.affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Terajima
authors.forename: John
authors.initials: J
authors.lastname: Cruz
authors.forename: Gregory
authors.initials: G
authors.lastname: Raines
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Kilpatrick
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D012900:Smallpox Vaccine / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D012900:Smallpox Vaccine