The Journal of Experimental Medicine
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Published online 31 March 2003 doi:10.1084/jem.20022222
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© Rockefeller University Press, 0022-1007/2003/4/927 $5.00
The Journal of Experimental Medicine, Volume 197, Number 7, 927-932

Brief Definitive Report

Quantitation of CD8+ T Cell Responses to Newly Identified HLA-A*0201–restricted T Cell Epitopes Conserved Among Vaccinia and Variola (Smallpox) Viruses

Masanori Terajima, John Cruz, Gregory Raines, Elizabeth D. Kilpatrick, Jeffrey S. Kennedy, Alan L. Rothman and Francis A. Ennis

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655

Address correspondence to Dr. Francis A. Ennis, Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655. Phone: 508-856-4182; Fax: 508-856-4890; E-mail: Francis.Ennis{at}umassmed.edu

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.

Key Words: immunologic memory • T lymphocyte epitopes • cytotoxic T lymphocytes • smallpox vaccine • major histocompatibility complex


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