Source:http://linkedlifedata.com/resource/pubmed/id/16441426
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2006-1-30
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pubmed:abstractText |
Peptide-MHC tetramers have been engineered to allow accurate detection of antigen-specific cytotoxic C lymphocytes (CTL) by flow cytometry. Here, we propose a novel use for peptide-MHC tetramers in the specific and sensitive analysis of the cytotoxic function of antigen-specific CTL by blocking MHC-restricted antigen-specific cytotoxicity. We found that pretreatment of ovalbumin (OVA)-specific CD8(+) CTL (OT-1 CTL), derived from OT-1 T-cell receptor (TCR)-transgenic mice, with OVA(257-264) peptide-H-2K(b) tetramer caused a marked inhibition of the cytotoxicity against OVA-expressing EG-7 tumor cells. OVA(257-264) peptide-H-2K(b) tetramer did not block the cytotoxicity mediated by 2C mouse (H-2(b))-derived CD8(+) CTL, which recognize allo (H-2L(d)) antigens. Moreover, OT-I CTL activity was not inhibited by an irrelevant HBV(208-216) peptide-H-2K(b) tetramer. These results indicate that the blocking of CTL activity with peptide-MHC tetramer was caused by interference with the interaction between the TCR and H-2K(b)-OVA(257-264) peptide complex, but not with the CD8-MHC class I interaction. The blocking activity of OVA(257-264) peptide-H-2K(b) tetramer was reversible because OT-I CTL pretreated with the tetramer recovered their cytotoxicity after culturing with interleukin-2 for 24 h. The same results were also demonstrated in freshly isolated, in vivo-primed OT-1 CTL sorted by the tetramer. These results demonstrate that peptide-MHC tetramer is a useful tool for defining MHC-restricted antigen-specific CTL function. Moreover, our finding implies that the measurement of CTL activity immediately after tetramer-guided sorting is not a suitable method for evaluating the function of in vivo-induced tetramer-positive CTL. We believe that the tetramer-blocking assay presented here will be useful for functionally monitor the induction of MHC-restricted antigen-specific CTL during vaccination therapy against tumor and infectious diseases.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/H-2Kb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1347-9032
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
148-54
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16441426-Animals,
pubmed-meshheading:16441426-Cytotoxicity, Immunologic,
pubmed-meshheading:16441426-H-2 Antigens,
pubmed-meshheading:16441426-Histocompatibility Antigens Class I,
pubmed-meshheading:16441426-Humans,
pubmed-meshheading:16441426-Mice,
pubmed-meshheading:16441426-Mice, Inbred BALB C,
pubmed-meshheading:16441426-Mice, Inbred C57BL,
pubmed-meshheading:16441426-Mice, Transgenic,
pubmed-meshheading:16441426-Ovalbumin,
pubmed-meshheading:16441426-Peptide Fragments,
pubmed-meshheading:16441426-Receptors, Antigen, T-Cell,
pubmed-meshheading:16441426-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:16441426-Thymoma,
pubmed-meshheading:16441426-Tumor Cells, Cultured
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pubmed:year |
2006
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pubmed:articleTitle |
Tetramer-blocking assay for defining antigen-specific cytotoxic T lymphocytes using peptide-MHC tetramer.
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pubmed:affiliation |
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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