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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0021083,
umls-concept:C0030956,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0205245,
umls-concept:C0205419,
umls-concept:C0385723,
umls-concept:C1332717,
umls-concept:C1334510,
umls-concept:C1413244,
umls-concept:C1521970,
umls-concept:C1704419,
umls-concept:C1706438,
umls-concept:C2349975,
umls-concept:C2698600
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pubmed:issue |
2
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pubmed:dateCreated |
1999-2-10
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pubmed:abstractText |
In the present study, we show that a singly substituted peptide derived from the epitope MART1(27-35) and containing a Leu in position 1 (LAGIGILTV; 1L) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions. 1L-specific CTLs can be raised from peripheral blood of HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MART1(27-35) when compared with CTL variable raised to parental peptide from the same patients. More importantly, anti-1L but not anti-native T cells display high levels of interferon gamma production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of MART1(27-35) natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable beta usage suggests that the native and 1L peptides stimulate different components of the MART1(27-35)-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth.
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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/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/MART-1-Melan-A(27-35) epitope,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
301-6
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9927036-CD8-Positive T-Lymphocytes,
pubmed-meshheading:9927036-Epitopes,
pubmed-meshheading:9927036-HLA-A2 Antigen,
pubmed-meshheading:9927036-Humans,
pubmed-meshheading:9927036-Immunization,
pubmed-meshheading:9927036-Immunotherapy,
pubmed-meshheading:9927036-Interferon-gamma,
pubmed-meshheading:9927036-Interleukin-2,
pubmed-meshheading:9927036-Melanoma,
pubmed-meshheading:9927036-Neoplasm Proteins,
pubmed-meshheading:9927036-Receptors, Antigen, T-Cell, alpha-beta
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pubmed:year |
1999
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pubmed:articleTitle |
A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy.
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pubmed:affiliation |
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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