MHC-I-restricted epitopes conserved among variola and other related orthopoxviruses are recognized by T cells 30 years after vaccination.
It is many years since the general population has been vaccinated against smallpox virus. Here, we report that human leukocyte antigen (HLA) class I restricted T cell epitopes can be recognized more than 30 years after vaccination. Using bioinformatic methods, we predicted 177 potential cytotoxic T lymphocyte epitopes. Eight epitopes were confirmed to stimulate IFN-gamma release by T cells in smallpox-vaccinated subjects. The epitopes were restricted by five supertypes (HLA-A1, -A2, -A24 -A26 and -B44). Significant T cell responses were detected against 8 of 45 peptides with an HLA class I affinity of K(D) less than or equal to 5 nM, whereas no T cell responses were detected against 60 peptides with an HLA affinity of K(D) more than 5 nM. All epitopes were fully conserved in seven variola, vaccinia and cowpox strains. Knowledge of the long-term response to smallpox vaccination may lead to a better understanding of poxvirus immunity and may aid in the development of new improved vaccines and diagnostic tools.
Tang
S T
ST
Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark.
Wang
M
M
Lamberth
K
K
Harndahl
M
M
Dziegiel
M H
MH
Claesson
M H
MH
Buus
S
S
Lund
O
O
D000328:Adult; D000368:Aged; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018155:Orthopoxvirus / Q000276:immunology*; D012900:Smallpox Vaccine / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D012900:Smallpox Vaccine; D007371:Interferon-gamma
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