Document Detail


GM-CSF production allows the identification of immunoprevalent antigens recognized by human CD4+ T cells following smallpox vaccination.
MedLine Citation:
PMID:  21931646     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.
Authors:
Valeria Judkowski; Alcinette Bunying; Feng Ge; Jon R Appel; Kingyee Law; Atima Sharma; Claudia Raja-Gabaglia; Patricia Norori; Radleigh G Santos; Marc A Giulianotti; Mark K Slifka; Daniel C Douek; Barney S Graham; Clemencia Pinilla
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-09
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-09-20     Completed Date:  2012-03-01     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24091     Citation Subset:  IM    
Affiliation:
Torrey Pines Institute for Molecular Studies, San Diego, California, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Antigen-Presenting Cells / immunology,  metabolism
Antigens / immunology*
Antigens, Viral / immunology
CD4-Positive T-Lymphocytes / immunology*,  metabolism
CD8-Positive T-Lymphocytes / immunology,  metabolism
Cell Line
Cells, Cultured
Granulocyte-Macrophage Colony-Stimulating Factor / immunology*,  metabolism
HLA-DR Antigens / immunology,  metabolism
Humans
Interferon-gamma / immunology,  metabolism
Smallpox / immunology
Smallpox Vaccine / immunology*
Tumor Necrosis Factor-alpha / immunology,  metabolism
Vaccination
Vaccinia / immunology
Vaccinia virus / immunology
Grant Support
ID/Acronym/Agency:
HHSN266200400080C/N01-AI-40080/AI/NIAID NIH HHS; R44 AI079898/AI/NIAID NIH HHS; R44 AI079898/AI/NIAID NIH HHS; RR00163/RR/NCRR NIH HHS; U01 AI082196/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens; 0/Antigens, Viral; 0/HLA-DR Antigens; 0/Smallpox Vaccine; 0/Tumor Necrosis Factor-alpha; 82115-62-6/Interferon-gamma; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor
Comments/Corrections

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