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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action</title><author><name sortKey="Lev, Avital" sort="Lev, Avital" uniqKey="Lev A" first="Avital" last="Lev">Avital Lev</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Princiotta, Michael F" sort="Princiotta, Michael F" uniqKey="Princiotta M" first="Michael F." last="Princiotta">Michael F. Princiotta</name><affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>State University of New York Upstate Medical Center</institution>, Syracuse, NY 13210;</nlm:aff></affiliation></author><author><name sortKey="Zanker, Damian" sort="Zanker, Damian" uniqKey="Zanker D" first="Damian" last="Zanker">Damian Zanker</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">T Cell Laboratory, Melbourne Centre for Clinical Sciences,<institution>Ludwig Institute for Cancer Research</institution>, Austin Health, Heidelberg, Victoria 3050,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Takeda, Kazuyo" sort="Takeda, Kazuyo" uniqKey="Takeda K" first="Kazuyo" last="Takeda">Kazuyo Takeda</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Gibbs, James S" sort="Gibbs, James S" uniqKey="Gibbs J" first="James S." last="Gibbs">James S. Gibbs</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Kumagai, Chiharu" sort="Kumagai, Chiharu" uniqKey="Kumagai C" first="Chiharu" last="Kumagai">Chiharu Kumagai</name><affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>State University of New York Upstate Medical Center</institution>, Syracuse, NY 13210;</nlm:aff></affiliation></author><author><name sortKey="Waffarn, Elizabeth" sort="Waffarn, Elizabeth" uniqKey="Waffarn E" first="Elizabeth" last="Waffarn">Elizabeth Waffarn</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Dolan, Brian P" sort="Dolan, Brian P" uniqKey="Dolan B" first="Brian P." last="Dolan">Brian P. Dolan</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Burgevin, Anne" sort="Burgevin, Anne" uniqKey="Burgevin A" first="Anne" last="Burgevin">Anne Burgevin</name><affiliation><nlm:aff id="aff4"><institution>Institut National de la Santé et de la Recherche Médicale</institution>, Paris,<country>France</country> 75743</nlm:aff></affiliation></author><author><name sortKey="Van Endert, Peter" sort="Van Endert, Peter" uniqKey="Van Endert P" first="Peter" last="Van Endert">Peter Van Endert</name><affiliation><nlm:aff id="aff4"><institution>Institut National de la Santé et de la Recherche Médicale</institution>, Paris,<country>France</country> 75743</nlm:aff></affiliation></author><author><name sortKey="Chen, Weisan" sort="Chen, Weisan" uniqKey="Chen W" first="Weisan" last="Chen">Weisan Chen</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">T Cell Laboratory, Melbourne Centre for Clinical Sciences,<institution>Ludwig Institute for Cancer Research</institution>, Austin Health, Heidelberg, Victoria 3050,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Bennink, Jack R" sort="Bennink, Jack R" uniqKey="Bennink J" first="Jack R." last="Bennink">Jack R. Bennink</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Yewdell, Jonathan W" sort="Yewdell, Jonathan W" uniqKey="Yewdell J" first="Jonathan W." last="Yewdell">Jonathan W. Yewdell</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20351281</idno><idno type="pmc">2872426</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872426</idno><idno type="RBID">PMC:2872426</idno><idno type="doi">10.1073/pnas.0910997107</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">001B38</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B38</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action</title><author><name sortKey="Lev, Avital" sort="Lev, Avital" uniqKey="Lev A" first="Avital" last="Lev">Avital Lev</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Princiotta, Michael F" sort="Princiotta, Michael F" uniqKey="Princiotta M" first="Michael F." last="Princiotta">Michael F. Princiotta</name><affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>State University of New York Upstate Medical Center</institution>, Syracuse, NY 13210;</nlm:aff></affiliation></author><author><name sortKey="Zanker, Damian" sort="Zanker, Damian" uniqKey="Zanker D" first="Damian" last="Zanker">Damian Zanker</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">T Cell Laboratory, Melbourne Centre for Clinical Sciences,<institution>Ludwig Institute for Cancer Research</institution>, Austin Health, Heidelberg, Victoria 3050,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Takeda, Kazuyo" sort="Takeda, Kazuyo" uniqKey="Takeda K" first="Kazuyo" last="Takeda">Kazuyo Takeda</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Gibbs, James S" sort="Gibbs, James S" uniqKey="Gibbs J" first="James S." last="Gibbs">James S. Gibbs</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Kumagai, Chiharu" sort="Kumagai, Chiharu" uniqKey="Kumagai C" first="Chiharu" last="Kumagai">Chiharu Kumagai</name><affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>State University of New York Upstate Medical Center</institution>, Syracuse, NY 13210;</nlm:aff></affiliation></author><author><name sortKey="Waffarn, Elizabeth" sort="Waffarn, Elizabeth" uniqKey="Waffarn E" first="Elizabeth" last="Waffarn">Elizabeth Waffarn</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Dolan, Brian P" sort="Dolan, Brian P" uniqKey="Dolan B" first="Brian P." last="Dolan">Brian P. Dolan</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Burgevin, Anne" sort="Burgevin, Anne" uniqKey="Burgevin A" first="Anne" last="Burgevin">Anne Burgevin</name><affiliation><nlm:aff id="aff4"><institution>Institut National de la Santé et de la Recherche Médicale</institution>, Paris,<country>France</country> 75743</nlm:aff></affiliation></author><author><name sortKey="Van Endert, Peter" sort="Van Endert, Peter" uniqKey="Van Endert P" first="Peter" last="Van Endert">Peter Van Endert</name><affiliation><nlm:aff id="aff4"><institution>Institut National de la Santé et de la Recherche Médicale</institution>, Paris,<country>France</country> 75743</nlm:aff></affiliation></author><author><name sortKey="Chen, Weisan" sort="Chen, Weisan" uniqKey="Chen W" first="Weisan" last="Chen">Weisan Chen</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">T Cell Laboratory, Melbourne Centre for Clinical Sciences,<institution>Ludwig Institute for Cancer Research</institution>, Austin Health, Heidelberg, Victoria 3050,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Bennink, Jack R" sort="Bennink, Jack R" uniqKey="Bennink J" first="Jack R." last="Bennink">Jack R. Bennink</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Yewdell, Jonathan W" sort="Yewdell, Jonathan W" uniqKey="Yewdell J" first="Jonathan W." last="Yewdell">Jonathan W. Yewdell</name><affiliation><nlm:aff id="aff1">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8<sup>+</sup> T cells. Cells typically express ∼100,000 class I molecules, or ∼1 per 30,000 cellular proteins. Given “one protein, one peptide” representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products.</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">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20351281</article-id><article-id pub-id-type="pmc">2872426</article-id><article-id pub-id-type="publisher-id">200910997</article-id><article-id pub-id-type="doi">10.1073/pnas.0910997107</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Immunology</subject></subj-group></subj-group></article-categories><title-group><article-title>Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lev</surname><given-names>Avital</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Princiotta</surname><given-names>Michael F.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zanker</surname><given-names>Damian</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Takeda</surname><given-names>Kazuyo</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gibbs</surname><given-names>James S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kumagai</surname><given-names>Chiharu</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Waffarn</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dolan</surname><given-names>Brian P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Burgevin</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Van Endert</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Weisan</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bennink</surname><given-names>Jack R.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yewdell</surname><given-names>Jonathan W.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,<institution>National Institutes of Health</institution>, Bethesda, MD 20892;</aff><aff id="aff2"><sup>b</sup>Department of Microbiology and Immunology,<institution>State University of New York Upstate Medical Center</institution>, Syracuse, NY 13210;</aff><aff id="aff3"><sup>c</sup>T Cell Laboratory, Melbourne Centre for Clinical Sciences,<institution>Ludwig Institute for Cancer Research</institution>, Austin Health, Heidelberg, Victoria 3050,<country>Australia</country>; and</aff><aff id="aff4"><sup>d</sup><institution>Institut National de la Santé et de la Recherche Médicale</institution>, Paris,<country>France</country> 75743</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence should be addressed. E-mail: <email>jyewdell@nih.gov</email>.</corresp><fn fn-type="edited-by"><p>Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 4, 2010 (received for review September 24, 2009)</p></fn><fn fn-type="con"><p>Author contributions: A.L., M.P., J.B., and J.Y. designed research; A.L., M.P., D.Z., K.T., J.G., C.K., L.W., B.D., A.B., P.E., and W.C. performed research; J.G. contributed new reagents/analytic tools; A.L., J.B., M.P., and J.Y. analyzed data; and A.L. and J.Y. wrote the paper.</p></fn></author-notes><pub-date pub-type="epub"><day>29</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>13</day><month>4</month><year>2010</year></pub-date><volume>107</volume><issue>15</issue><fpage>6964</fpage><lpage>6969</lpage><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.200910997.pdf"></self-uri><abstract><p>MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8<sup>+</sup> T cells. Cells typically express ∼100,000 class I molecules, or ∼1 per 30,000 cellular proteins. Given “one protein, one peptide” representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products.</p></abstract><kwd-group><kwd>MHC</kwd><kwd>peptide</kwd><kwd>translation</kwd><kwd>virus</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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