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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>
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