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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular mimicry of MAGE-A6 and <italic>Mycoplasma penetrans</italic> HF-2 epitopes in the induction of antitumor CD8<sup>+</sup> T-cell responses</title><author><name sortKey="Vujanovic, Lazar" sort="Vujanovic, Lazar" uniqKey="Vujanovic L" first="Lazar" last="Vujanovic">Lazar Vujanovic</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Shi, Jian" sort="Shi, Jian" uniqKey="Shi J" first="Jian" last="Shi">Jian Shi</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Kirkwood, John M" sort="Kirkwood, John M" uniqKey="Kirkwood J" first="John M" last="Kirkwood">John M. Kirkwood</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Storkus, Walter J" sort="Storkus, Walter J" uniqKey="Storkus W" first="Walter J" last="Storkus">Walter J. Storkus</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0003"><institution>University of Pittsburgh School of Medicine; Department of Immunology</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0004"><institution>University of Pittsburgh School of Medicine; Department of Dermatology</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Butterfield, Lisa H" sort="Butterfield, Lisa H" uniqKey="Butterfield L" first="Lisa H" last="Butterfield">Lisa H. Butterfield</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0003"><institution>University of Pittsburgh School of Medicine; Department of Immunology</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0005"><institution>University of Pittsburgh School of Medicine; Department of Surgery</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25960935</idno><idno type="pmc">4368152</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368152</idno><idno type="RBID">PMC:4368152</idno><idno type="doi">10.4161/21624011.2014.954501</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000114</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000114</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Molecular mimicry of MAGE-A6 and <italic>Mycoplasma penetrans</italic> HF-2 epitopes in the induction of antitumor CD8<sup>+</sup> T-cell responses</title><author><name sortKey="Vujanovic, Lazar" sort="Vujanovic, Lazar" uniqKey="Vujanovic L" first="Lazar" last="Vujanovic">Lazar Vujanovic</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Shi, Jian" sort="Shi, Jian" uniqKey="Shi J" first="Jian" last="Shi">Jian Shi</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Kirkwood, John M" sort="Kirkwood, John M" uniqKey="Kirkwood J" first="John M" last="Kirkwood">John M. Kirkwood</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Storkus, Walter J" sort="Storkus, Walter J" uniqKey="Storkus W" first="Walter J" last="Storkus">Walter J. Storkus</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0003"><institution>University of Pittsburgh School of Medicine; Department of Immunology</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0004"><institution>University of Pittsburgh School of Medicine; Department of Dermatology</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Butterfield, Lisa H" sort="Butterfield, Lisa H" uniqKey="Butterfield L" first="Lisa H" last="Butterfield">Lisa H. Butterfield</name><affiliation><nlm:aff id="af0001"><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0002"><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0003"><institution>University of Pittsburgh School of Medicine; Department of Immunology</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="af0005"><institution>University of Pittsburgh School of Medicine; Department of Surgery</institution>; Pittsburgh, PA<country>USA</country></nlm:aff></affiliation></author></analytic><series><title level="j">Oncoimmunology</title><idno type="ISSN">2162-4011</idno><idno type="eISSN">2162-402X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A promising vaccine strategy for the treatment of cancer involves the use of vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cells. Previously, we reported that a MAGE-A6-derived peptide (MAGE-A6<sub>172–187</sub>) and its highly-immunogenic and cross-reactive homolog derived from <italic>Mycoplasma penetrans</italic> HF-2 permease (HF-2<sub>216–229</sub>) are promiscuously presented by multiple HLA-DR alleles to responder CD4<sup>+</sup> T-cells obtained from healthy donors and melanoma patients. Here, we investigated whether these same peptides could concomitantly stimulate cross-reactive MAGE-A6-specific CD8<sup>+</sup> T-cell responses <italic>in vitro</italic> using cells isolated from HLA-A*0201 (HLA-A2)<sup>+</sup> healthy individuals and patients with melanoma. We now show that MAGE-A6<sub>172–187</sub> and, even more so, HF-2<sub>216–229</sub>, induce memory CD8<sup>+</sup> T cells that recognize HLA-A2<sup>+</sup> MAGE-A6<sup>+</sup> tumor target cells. The immunogenicity of these peptides was at least partially attributed to their embedded MAGE-A6<sub>176–185</sub> and HF-2<sub>220–229</sub> “homologous” sequences. The functional avidity of HF-2<sub>216–229</sub> peptide-primed CD8<sup>+</sup> T cells for the MAGE-A6<sub>172–187</sub> peptide was more than 100-fold greater than that of CD8<sup>+</sup> T cells primed with the corresponding MAGE-A6 peptide. Additionally, these 2 peptides were recognized in interferon γ (IFNγ) and granzyme B ELISPOT assays by CD8<sup>+</sup> T-cell clones displaying variable T-cell receptor (TCR) Vβ usage. These data suggest that the immune cross-reactivity of the MAGE-A6<sub>172–187</sub> and HF-2<sub>216–229</sub> peptides extends to CD8<sup>+</sup> T cells, at least in HLA-A2<sup>+</sup> donors, and supports the potential translational utility of these epitopes in clinical vaccine formulations and for immunomonitoring of cancer patients.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncoimmunology</journal-id><journal-id journal-id-type="iso-abbrev">Oncoimmunology</journal-id><journal-id journal-id-type="pmc">KONI</journal-id><journal-title-group><journal-title>Oncoimmunology</journal-title></journal-title-group><issn pub-type="ppub">2162-4011</issn><issn pub-type="epub">2162-402X</issn><publisher><publisher-name>Taylor & Francis</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25960935</article-id><article-id pub-id-type="pmc">4368152</article-id><article-id pub-id-type="publisher-id">954501</article-id><article-id pub-id-type="doi">10.4161/21624011.2014.954501</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject></subj-group></article-categories><title-group><article-title>Molecular mimicry of MAGE-A6 and <italic>Mycoplasma penetrans</italic> HF-2 epitopes in the induction of antitumor CD8<sup>+</sup> T-cell responses</article-title><alt-title alt-title-type="running-title">Eliciting tumor-specific CTLs using epitope mimics</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Vujanovic</surname><given-names>Lazar</given-names></name><xref ref-type="aff" rid="af0001"><sup>1</sup></xref><xref ref-type="aff" rid="af0002"><sup>2</sup></xref><xref ref-type="corresp" rid="an0001"></xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Jian</given-names></name><xref ref-type="aff" rid="af0001"><sup>1</sup></xref><xref ref-type="aff" rid="af0002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kirkwood</surname><given-names>John M</given-names></name><xref ref-type="aff" rid="af0001"><sup>1</sup></xref><xref ref-type="aff" rid="af0002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Storkus</surname><given-names>Walter J</given-names></name><xref ref-type="aff" rid="af0001"><sup>1</sup></xref><xref ref-type="aff" rid="af0003"><sup>3</sup></xref><xref ref-type="aff" rid="af0004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Butterfield</surname><given-names>Lisa H</given-names></name><xref ref-type="aff" rid="af0001"><sup>1</sup></xref><xref ref-type="aff" rid="af0002"><sup>2</sup></xref><xref ref-type="aff" rid="af0003"><sup>3</sup></xref><xref ref-type="aff" rid="af0005"><sup>5</sup></xref></contrib><aff id="af0001"><label>1</label><institution>University of Pittsburgh Cancer Institute</institution>; Pittsburgh, PA<country>USA</country></aff><aff id="af0002"><label>2</label><institution>University of Pittsburgh School of Medicine; Department of Medicine</institution>; Pittsburgh, PA<country>USA</country></aff><aff id="af0003"><label>3</label><institution>University of Pittsburgh School of Medicine; Department of Immunology</institution>; Pittsburgh, PA<country>USA</country></aff><aff id="af0004"><label>4</label><institution>University of Pittsburgh School of Medicine; Department of Dermatology</institution>; Pittsburgh, PA<country>USA</country></aff><aff id="af0005"><label>5</label><institution>University of Pittsburgh School of Medicine; Department of Surgery</institution>; Pittsburgh, PA<country>USA</country></aff></contrib-group><author-notes><corresp id="an0001"><label>*</label>Correspondence to: Lazar Vujanovic; Email: <email xlink:href="vujanovicl@upmc.edu">vujanovicl@upmc.edu</email></corresp><fn><p><bold>Summary sentence:</bold> This study shows that epitopes from Mycoplasma penetrans, a common pathogen, are cross-reactive with epitopes derived from MAGE-A6 and may be important cancer immunotherapy tools.</p></fn></author-notes><pub-date pub-type="epub"><day>14</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="collection"><year>2014</year></pub-date><volume>3</volume><issue>8</issue><elocation-id seq="8">e954501</elocation-id><history><date date-type="received"><day>25</day><month>3</month><year>2014</year></date><date date-type="rev-request"><day>08</day><month>7</month><year>2014</year></date><date date-type="accepted"><day>11</day><month>7</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 Taylor & Francis Group, LLC</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>2014 Taylor & Francis Group, LLC</copyright-holder></permissions><self-uri content-type="pdf" xlink:href="koni-03-e954501.pdf"></self-uri><abstract><p>A promising vaccine strategy for the treatment of cancer involves the use of vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cells. Previously, we reported that a MAGE-A6-derived peptide (MAGE-A6<sub>172–187</sub>) and its highly-immunogenic and cross-reactive homolog derived from <italic>Mycoplasma penetrans</italic> HF-2 permease (HF-2<sub>216–229</sub>) are promiscuously presented by multiple HLA-DR alleles to responder CD4<sup>+</sup> T-cells obtained from healthy donors and melanoma patients. Here, we investigated whether these same peptides could concomitantly stimulate cross-reactive MAGE-A6-specific CD8<sup>+</sup> T-cell responses <italic>in vitro</italic> using cells isolated from HLA-A*0201 (HLA-A2)<sup>+</sup> healthy individuals and patients with melanoma. We now show that MAGE-A6<sub>172–187</sub> and, even more so, HF-2<sub>216–229</sub>, induce memory CD8<sup>+</sup> T cells that recognize HLA-A2<sup>+</sup> MAGE-A6<sup>+</sup> tumor target cells. The immunogenicity of these peptides was at least partially attributed to their embedded MAGE-A6<sub>176–185</sub> and HF-2<sub>220–229</sub> “homologous” sequences. The functional avidity of HF-2<sub>216–229</sub> peptide-primed CD8<sup>+</sup> T cells for the MAGE-A6<sub>172–187</sub> peptide was more than 100-fold greater than that of CD8<sup>+</sup> T cells primed with the corresponding MAGE-A6 peptide. Additionally, these 2 peptides were recognized in interferon γ (IFNγ) and granzyme B ELISPOT assays by CD8<sup>+</sup> T-cell clones displaying variable T-cell receptor (TCR) Vβ usage. These data suggest that the immune cross-reactivity of the MAGE-A6<sub>172–187</sub> and HF-2<sub>216–229</sub> peptides extends to CD8<sup>+</sup> T cells, at least in HLA-A2<sup>+</sup> donors, and supports the potential translational utility of these epitopes in clinical vaccine formulations and for immunomonitoring of cancer patients.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords</title><kwd>CD8<sup>+</sup> T-cell</kwd><kwd>epitope mimic</kwd><kwd>MAGE-A6</kwd><kwd>melanoma</kwd><kwd><italic>Mycoplasma penetrans</italic></kwd></kwd-group><kwd-group kwd-group-type="author"><title>Abbreviations:</title><kwd>AdV, recombinant adenoviral vector</kwd><kwd>APC, antigen presenting cell</kwd><kwd>CTL, cytotoxic T lymphocyte</kwd><kwd>EBV, Epstein-Barr virus</kwd><kwd>FBS, fetal bovine serum</kwd><kwd>HD, healthy donor</kwd><kwd>HLA, human leukocyte antigen</kwd><kwd>HPLC, high-performance liquid chromatography</kwd><kwd>iDC, immature dendritic cells</kwd><kwd>IVS, in vitro stimulation</kwd><kwd>MACS, Magnetic-Activated Cell Sorting</kwd><kwd>mDC, mature dendritic cells</kwd><kwd>MOI, multiplicity of infection</kwd><kwd>PBMC, peripheral blood mononuclear cell</kwd><kwd>PFU, plaque forming units</kwd><kwd>RT-PCR, reverse transcription polymerase chain reaction</kwd><kwd>TAA, tumor associated antigen</kwd><kwd>TCM, T cell media</kwd><kwd>TCR, T-cell receptor</kwd></kwd-group><counts><fig-count count="5"></fig-count><table-count count="2"></table-count><ref-count count="53"></ref-count><page-count count="13"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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