| Hierarchy of alpha fetoprotein (AFP)-specific T cell responses in subjects with AFP-positive hepatocellular cancer. | |
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MedLine Citation:
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PMID: 16785570 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We identified a series of immunodominant and subdominant epitopes from alpha fetoprotein (AFP), restricted by HLA-A*0201, which are recognized by the human T cell repertoire. The four immunodominant epitopes have been tested for immunogenicity in vivo, in HLA-A*0201+AFP+ advanced stage hepatocellular cancer (HCC) patients, and have activated and expanded AFP-specific IFN-gamma-producing T cells in these patients, despite high serum levels of this self Ag. Here, we have examined the frequency, function, and avidity of the T cells specific for subdominant epitopes from AFP. We find that T cells specific for several of these epitopes are of similar or higher avidity than those specific for immunodominant epitopes. We then tested the peripheral blood of subjects ex vivo with different levels of serum AFP for the hierarchy of response to epitopes from this Ag and find that HCC patients have detectable frequencies of circulating IFN-gamma-producing AFP-specific CD8+ T cells to both immunodominant and subdominant epitopes. We find the immunodominant and subdominant peptide-specific T cells to be differentially expanded with different modes of Ag presentation. Whereas spontaneous and AFP protein-stimulated responses show evidence for immunodominance, AdVhAFP-transduced dendritic cell-stimulated responses were broader and not skewed. Importantly, these data identify subdominant epitopes from AFP that can activate high-avidity T cells, and that can be detected and expanded in HCC subjects. These subdominant epitope-specific T cells can also recognize tumor cells and may be important therapeutically. |
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Authors:
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Yang Liu; Sean Daley; Viktoria N Evdokimova; David D Zdobinski; Douglas M Potter; Lisa H Butterfield |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 177 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-20 Completed Date: 2006-08-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 712-21 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Aged Antigen Presentation / genetics, immunology* CD8-Positive T-Lymphocytes / immunology*, metabolism*, pathology Carcinoma, Hepatocellular / immunology*, metabolism, pathology Cell Proliferation Cells, Cultured Cytotoxicity Tests, Immunologic Dendritic Cells / immunology, metabolism Epitopes, T-Lymphocyte / immunology, metabolism Humans Immunodominant Epitopes / immunology*, metabolism K562 Cells Liver Neoplasms / immunology*, metabolism, pathology Lymphocyte Activation / genetics, immunology Lymphocyte Count Male Middle Aged Peptide Fragments / chemical synthesis, immunology, metabolism Protein Binding / immunology Transduction, Genetic alpha-Fetoproteins / biosynthesis*, immunology* |
| Chemical | |
Reg. No./Substance:
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0/Epitopes, T-Lymphocyte; 0/Immunodominant Epitopes; 0/Peptide Fragments; 0/alpha-Fetoproteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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