Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.

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.
AuthorsMasanori Terajima, John Cruz, Gregory Raines, Elizabeth D Kilpatrick, Jeffrey S Kennedy, Alan L Rothman, Francis A Ennis
JournalThe Journal of experimental medicine (J Exp Med) Vol. 197 Issue 7 Pg. 927-32 (Apr 7 2003) ISSN: 0022-1007 [Print] United States
PMID12668642 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Smallpox Vaccine
  • CD8-Positive T-Lymphocytes (immunology)
  • Cell Line
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens (immunology)
  • Humans
  • Immunologic Memory
  • Smallpox Vaccine (immunology)
  • T-Lymphocytes, Cytotoxic (immunology)
  • Vaccinia virus (immunology)

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