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rdf:type |
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lifeskim:mentions |
umls-concept:C0003175,
umls-concept:C0003320,
umls-concept:C0039194,
umls-concept:C0040549,
umls-concept:C0085358,
umls-concept:C1332714,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1553423,
umls-concept:C1706438,
umls-concept:C1708111,
umls-concept:C2698600
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pubmed:issue |
6
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pubmed:dateCreated |
2008-5-20
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pubmed:abstractText |
The lethal toxin produced by Bacillus anthracis is a bipartite toxin in which the first protein, protective antigen (PA), transports the second protein, lethal factor, across the host cell membrane. We have previously shown that CD8(+) T-cell epitopes fused to a nontoxic derivative of lethal factor (LFn) are delivered into the host cell cytosol in a PA-dependent manner. Delivery of these antigens targets them to the intracellular major histocompatibility complex (MHC) class I processing and presentation pathway and leads to the stimulation of antigen-specific CD8(+) T cells in vivo. In this report, we describe the generation and characterization of LFn fusion proteins that include not only a CD8(+) T-cell epitope but also a CD4(+) T-cell epitope. We first show that these fusion proteins induce antigen-specific CD4(+) T-cell responses following incubation with dendritic cells in vitro or injection into mice. Stimulation of CD4(+) T cells by LFn fusion proteins does not require PA but is enhanced by PA in vitro. We also show that a single LFn fusion protein and PA can deliver antigen to both the MHC class II and the MHC class I pathways, resulting in the simultaneous induction of antigen-specific CD4(+) T cells and antigen-specific CD8(+) T cells in the same mouse. These results suggest that this toxin delivery system is capable of stimulating protective immune responses where effective immunization requires stimulation of both classes of T cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-10377103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-10837060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-10884430,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11113126,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11602637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11684289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11700562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11790132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11823503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11861614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-11997439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-12414723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-12551953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-12700348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-12942084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-15286726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-15528345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-15549606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-15689409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-15964481,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-1787799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-2467303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-2895741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-7968541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-8051159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-8287475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-8429009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-8476559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-8901616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-9342362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-9453617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-9462514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-9553774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-9597133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18347032-9746566
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1098-5522
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
76
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2603-11
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18347032-Animals,
pubmed-meshheading:18347032-Antigens, Bacterial,
pubmed-meshheading:18347032-Bacillus anthracis,
pubmed-meshheading:18347032-Bacterial Toxins,
pubmed-meshheading:18347032-CD4-Positive T-Lymphocytes,
pubmed-meshheading:18347032-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18347032-Dendritic Cells,
pubmed-meshheading:18347032-Epitopes,
pubmed-meshheading:18347032-Genes, MHC Class I,
pubmed-meshheading:18347032-Genes, MHC Class II,
pubmed-meshheading:18347032-Interferon-gamma,
pubmed-meshheading:18347032-Lymphocyte Activation,
pubmed-meshheading:18347032-Mice,
pubmed-meshheading:18347032-Mice, Inbred C57BL,
pubmed-meshheading:18347032-Mice, Transgenic,
pubmed-meshheading:18347032-Recombinant Proteins,
pubmed-meshheading:18347032-Specific Pathogen-Free Organisms
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pubmed:year |
2008
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pubmed:articleTitle |
Both CD4+ and CD8+ T cells respond to antigens fused to anthrax lethal toxin.
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pubmed:affiliation |
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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