Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy.
Identifieur interne : 000A68 ( Main/Exploration ); précédent : 000A67; suivant : 000A69Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy.
Auteurs : Alejandro Sanz-Bravo [Espagne] ; Adrian Martín-Esteban [Espagne] ; Jonas J W. Kuiper [Pays-Bas] ; Marina García-Peydr [Espagne] ; Eilon Barnea [Israël] ; Arie Admon [Israël] ; José A. L Pez De Castro [Espagne]Source :
- Molecular & cellular proteomics : MCP [ 1535-9484 ] ; 2018.
Descripteurs français
- KwdFr :
- Allèles, Aminopeptidases (), Aminopeptidases (génétique), Aminopeptidases (métabolisme), Antigènes HLA-A (génétique), Choriorétinite (génétique), Humains, Interactions hydrophobes et hydrophiles, Ligands, Lignée cellulaire, Peptides (métabolisme), Protéome (génétique), Prédisposition génétique à une maladie.
- MESH :
English descriptors
- KwdEn :
- Alleles, Aminopeptidases (chemistry), Aminopeptidases (genetics), Aminopeptidases (metabolism), Birdshot Chorioretinopathy, Cell Line, Chorioretinitis (genetics), Genetic Predisposition to Disease, HLA-A Antigens (genetics), Humans, Hydrophobic and Hydrophilic Interactions, Ligands, Peptides (metabolism), Proteome (genetics).
- MESH :
- chemical , chemistry : Aminopeptidases.
- chemical , genetics : Aminopeptidases, HLA-A Antigens, Proteome.
- chemical , metabolism : Aminopeptidases, Peptides.
- genetics : Chorioretinitis.
- Alleles, Birdshot Chorioretinopathy, Cell Line, Genetic Predisposition to Disease, Humans, Hydrophobic and Hydrophilic Interactions, Ligands.
Abstract
Virtually all patients of the rare inflammatory eye disease birdshot chorioretinopathy (BSCR) carry the HLA-A*29:02 allele. BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. To investigate the relationship between both risk factors we employed label-free quantitative mass spectrometry to characterize the effects of ERAP2 on the A*29:02-bound peptidome. An ERAP2-negative cell line was transduced with lentiviral constructs containing GFP-ERAP2 or GFP alone, and the A*29:02 peptidomes from both transduced cells were compared. A similar analysis was performed with two additional A*29:02-positive, ERAP1-concordant, cell lines expressing or not ERAP2. In both comparisons the presence of ERAP2 affected the following features of the A*29:02 peptidome: 1) Length, with increased amounts of peptides >9-mers, and 2) N-terminal residues, with less ERAP2-susceptible and more hydrophobic ones. The paradoxical effects on peptide length suggest that unproductive binding to ERAP2 might protect some peptides from ERAP1 over-trimming. The influence on N-terminal residues can be explained by a direct effect of ERAP2 on trimming, without ruling out and improved processing in concert with ERAP1. The alterations in the A*29:02 peptidome suggest that the association of ERAP2 with BSCR is through its effects on peptide processing. These differ from those on the ankylosing spondylitis-associated HLA-B*27. Thus, ERAP2 alters the peptidome of distinct HLA molecules as a function of their specific binding preferences, influencing different pathological outcomes in an allele-dependent way.
DOI: 10.1074/mcp.RA118.000778
PubMed: 29769354
Affiliations:
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L Pez De Castro</name><affiliation wicri:level="2"><nlm:affiliation>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain; aldecastro@cbm.csic.es.</nlm:affiliation><country wicri:rule="url">Espagne</country><wicri:regionArea>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:29769354</idno><idno type="pmid">29769354</idno><idno type="doi">10.1074/mcp.RA118.000778</idno><idno type="wicri:Area/PubMed/Corpus">000901</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000901</idno><idno type="wicri:Area/PubMed/Curation">000901</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000901</idno><idno type="wicri:Area/PubMed/Checkpoint">000A17</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000A17</idno><idno type="wicri:Area/Ncbi/Merge">001E31</idno><idno type="wicri:Area/Ncbi/Curation">001E31</idno><idno type="wicri:Area/Ncbi/Checkpoint">001E31</idno><idno type="wicri:Area/Main/Merge">000A71</idno><idno type="wicri:Area/Main/Curation">000A68</idno><idno type="wicri:Area/Main/Exploration">000A68</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy.</title><author><name sortKey="Sanz Bravo, Alejandro" sort="Sanz Bravo, Alejandro" uniqKey="Sanz Bravo A" first="Alejandro" last="Sanz-Bravo">Alejandro Sanz-Bravo</name><affiliation wicri:level="2"><nlm:affiliation>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Martin Esteban, Adrian" sort="Martin Esteban, Adrian" uniqKey="Martin Esteban A" first="Adrian" last="Martín-Esteban">Adrian Martín-Esteban</name><affiliation wicri:level="2"><nlm:affiliation>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Kuiper, Jonas J W" sort="Kuiper, Jonas J W" uniqKey="Kuiper J" first="Jonas J W" last="Kuiper">Jonas J W. Kuiper</name><affiliation wicri:level="1"><nlm:affiliation>§Department of Ophthalmology, University Medical Center Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>§Department of Ophthalmology, University Medical Center Utrecht</wicri:regionArea><wicri:noRegion>University Medical Center Utrecht</wicri:noRegion></affiliation></author><author><name sortKey="Garcia Peydr, Marina" sort="Garcia Peydr, Marina" uniqKey="Garcia Peydr M" first="Marina" last="García-Peydr">Marina García-Peydr</name><affiliation wicri:level="2"><nlm:affiliation>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Barnea, Eilon" sort="Barnea, Eilon" uniqKey="Barnea E" first="Eilon" last="Barnea">Eilon Barnea</name><affiliation wicri:level="1"><nlm:affiliation>¶Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>¶Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000</wicri:regionArea><wicri:noRegion>Haifa 32000</wicri:noRegion></affiliation></author><author><name sortKey="Admon, Arie" sort="Admon, Arie" uniqKey="Admon A" first="Arie" last="Admon">Arie Admon</name><affiliation wicri:level="1"><nlm:affiliation>¶Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>¶Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000</wicri:regionArea><wicri:noRegion>Haifa 32000</wicri:noRegion></affiliation></author><author><name sortKey="L Pez De Castro, Jose A" sort="L Pez De Castro, Jose A" uniqKey="L Pez De Castro J" first="José A" last="L Pez De Castro">José A. L Pez De Castro</name><affiliation wicri:level="2"><nlm:affiliation>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain; aldecastro@cbm.csic.es.</nlm:affiliation><country wicri:rule="url">Espagne</country><wicri:regionArea>From the ‡Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region></placeName></affiliation></author></analytic><series><title level="j">Molecular & cellular proteomics : MCP</title><idno type="eISSN">1535-9484</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term><term>Aminopeptidases (chemistry)</term><term>Aminopeptidases (genetics)</term><term>Aminopeptidases (metabolism)</term><term>Birdshot Chorioretinopathy</term><term>Cell Line</term><term>Chorioretinitis (genetics)</term><term>Genetic Predisposition to Disease</term><term>HLA-A Antigens (genetics)</term><term>Humans</term><term>Hydrophobic and Hydrophilic Interactions</term><term>Ligands</term><term>Peptides (metabolism)</term><term>Proteome (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allèles</term><term>Aminopeptidases ()</term><term>Aminopeptidases (génétique)</term><term>Aminopeptidases (métabolisme)</term><term>Antigènes HLA-A (génétique)</term><term>Choriorétinite (génétique)</term><term>Humains</term><term>Interactions hydrophobes et hydrophiles</term><term>Ligands</term><term>Lignée cellulaire</term><term>Peptides (métabolisme)</term><term>Protéome (génétique)</term><term>Prédisposition génétique à une maladie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Aminopeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Aminopeptidases</term><term>HLA-A Antigens</term><term>Proteome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Aminopeptidases</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Chorioretinitis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Aminopeptidases</term><term>Antigènes HLA-A</term><term>Choriorétinite</term><term>Protéome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Aminopeptidases</term><term>Peptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Birdshot Chorioretinopathy</term><term>Cell Line</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Hydrophobic and Hydrophilic Interactions</term><term>Ligands</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Allèles</term><term>Aminopeptidases</term><term>Humains</term><term>Interactions hydrophobes et hydrophiles</term><term>Ligands</term><term>Lignée cellulaire</term><term>Prédisposition génétique à une maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Virtually all patients of the rare inflammatory eye disease birdshot chorioretinopathy (BSCR) carry the HLA-A*29:02 allele. BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. To investigate the relationship between both risk factors we employed label-free quantitative mass spectrometry to characterize the effects of ERAP2 on the A*29:02-bound peptidome. An ERAP2-negative cell line was transduced with lentiviral constructs containing GFP-ERAP2 or GFP alone, and the A*29:02 peptidomes from both transduced cells were compared. A similar analysis was performed with two additional A*29:02-positive, ERAP1-concordant, cell lines expressing or not ERAP2. In both comparisons the presence of ERAP2 affected the following features of the A*29:02 peptidome: 1) Length, with increased amounts of peptides >9-mers, and 2) N-terminal residues, with less ERAP2-susceptible and more hydrophobic ones. The paradoxical effects on peptide length suggest that unproductive binding to ERAP2 might protect some peptides from ERAP1 over-trimming. The influence on N-terminal residues can be explained by a direct effect of ERAP2 on trimming, without ruling out and improved processing in concert with ERAP1. The alterations in the A*29:02 peptidome suggest that the association of ERAP2 with BSCR is through its effects on peptide processing. These differ from those on the ankylosing spondylitis-associated HLA-B*27. Thus, ERAP2 alters the peptidome of distinct HLA molecules as a function of their specific binding preferences, influencing different pathological outcomes in an allele-dependent way.</div></front></TEI><affiliations><list><country><li>Espagne</li><li>Israël</li><li>Pays-Bas</li></country><region><li>Communauté de Madrid</li></region></list><tree><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Sanz Bravo, Alejandro" sort="Sanz Bravo, Alejandro" uniqKey="Sanz Bravo A" first="Alejandro" last="Sanz-Bravo">Alejandro Sanz-Bravo</name></region><name sortKey="Garcia Peydr, Marina" sort="Garcia Peydr, Marina" uniqKey="Garcia Peydr M" first="Marina" last="García-Peydr">Marina García-Peydr</name><name sortKey="L Pez De Castro, Jose A" sort="L Pez De Castro, Jose A" uniqKey="L Pez De Castro J" first="José A" last="L Pez De Castro">José A. L Pez De Castro</name><name sortKey="Martin Esteban, Adrian" sort="Martin Esteban, Adrian" uniqKey="Martin Esteban A" first="Adrian" last="Martín-Esteban">Adrian Martín-Esteban</name></country><country name="Pays-Bas"><noRegion><name sortKey="Kuiper, Jonas J W" sort="Kuiper, Jonas J W" uniqKey="Kuiper J" first="Jonas J W" last="Kuiper">Jonas J W. Kuiper</name></noRegion></country><country name="Israël"><noRegion><name sortKey="Barnea, Eilon" sort="Barnea, Eilon" uniqKey="Barnea E" first="Eilon" last="Barnea">Eilon Barnea</name></noRegion><name sortKey="Admon, Arie" sort="Admon, Arie" uniqKey="Admon A" first="Arie" last="Admon">Arie Admon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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