Predicting the effects of potentially therapeutic modified peptides on polyclonal T cell populations in a mouse model of multiple sclerosis.
Identifieur interne : 000576 ( Main/Exploration ); précédent : 000575; suivant : 000577Predicting the effects of potentially therapeutic modified peptides on polyclonal T cell populations in a mouse model of multiple sclerosis.
Auteurs : Evan L. Sauer [Australie] ; Elisabeth Trifilieff [France] ; Judith M. Greer [Australie]Source :
- Journal of neuroimmunology [ 1872-8421 ] ; 2017.
Descripteurs français
- KwdFr :
- ARN messager, Adjuvant Freund (toxicité), Animaux, Cellules présentatrices d'antigène (), Cellules présentatrices d'antigène (immunologie), Cytokines (génétique), Cytokines (métabolisme), Cytométrie en flux, Encéphalomyélite auto-immune expérimentale (), Encéphalomyélite auto-immune expérimentale (anatomopathologie), Encéphalomyélite auto-immune expérimentale (immunologie), Encéphalomyélite auto-immune expérimentale (traitement médicamenteux), Femelle, Fragments peptidiques (), Fragments peptidiques (génétique), Fragments peptidiques (immunologie), Fragments peptidiques (toxicité), Lymphocytes T (), Lymphocytes T (immunologie), Lymphocytes auxiliaires Th1 (), Modèles animaux de maladie humaine, Prolifération cellulaire (), Protéine protéolipidique myéline (), Protéine protéolipidique myéline (génétique), Protéine protéolipidique myéline (toxicité), Récepteur lymphocytaire T antigène, alpha-bêta (génétique), Récepteur lymphocytaire T antigène, alpha-bêta (métabolisme), Souris, Séquence d'acides aminés, Épitopes (), Épitopes (immunologie).
- MESH :
- anatomopathologie : Encéphalomyélite auto-immune expérimentale.
- génétique : Cytokines, Fragments peptidiques, Protéine protéolipidique myéline, Récepteur lymphocytaire T antigène, alpha-bêta.
- immunologie : Cellules présentatrices d'antigène, Encéphalomyélite auto-immune expérimentale, Fragments peptidiques, Lymphocytes T, Épitopes.
- métabolisme : Cytokines, Récepteur lymphocytaire T antigène, alpha-bêta.
- toxicité : Adjuvant Freund, Fragments peptidiques, Protéine protéolipidique myéline.
- traitement médicamenteux : Encéphalomyélite auto-immune expérimentale.
- ARN messager, Animaux, Cellules présentatrices d'antigène, Cytométrie en flux, Encéphalomyélite auto-immune expérimentale, Femelle, Fragments peptidiques, Lymphocytes T, Lymphocytes auxiliaires Th1, Modèles animaux de maladie humaine, Prolifération cellulaire, Protéine protéolipidique myéline, Souris, Séquence d'acides aminés, Épitopes.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antigen-Presenting Cells (drug effects), Antigen-Presenting Cells (immunology), Cell Proliferation (drug effects), Cytokines (genetics), Cytokines (metabolism), Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental (chemically induced), Encephalomyelitis, Autoimmune, Experimental (drug therapy), Encephalomyelitis, Autoimmune, Experimental (immunology), Encephalomyelitis, Autoimmune, Experimental (pathology), Epitopes (chemistry), Epitopes (immunology), Female, Flow Cytometry, Freund's Adjuvant (toxicity), Mice, Myelin Proteolipid Protein (chemistry), Myelin Proteolipid Protein (genetics), Myelin Proteolipid Protein (toxicity), Peptide Fragments (chemistry), Peptide Fragments (genetics), Peptide Fragments (immunology), Peptide Fragments (toxicity), RNA, Messenger, Receptors, Antigen, T-Cell, alpha-beta (genetics), Receptors, Antigen, T-Cell, alpha-beta (metabolism), T-Lymphocytes (drug effects), T-Lymphocytes (immunology), Th1 Cells (drug effects).
- MESH :
- chemical , chemistry : Epitopes, Myelin Proteolipid Protein, Peptide Fragments.
- chemical , genetics : Cytokines, Myelin Proteolipid Protein, Peptide Fragments, Receptors, Antigen, T-Cell, alpha-beta.
- chemically induced : Encephalomyelitis, Autoimmune, Experimental.
- drug effects : Antigen-Presenting Cells, Cell Proliferation, T-Lymphocytes, Th1 Cells.
- drug therapy : Encephalomyelitis, Autoimmune, Experimental.
- immunology : Antigen-Presenting Cells, Encephalomyelitis, Autoimmune, Experimental, Epitopes, Peptide Fragments, T-Lymphocytes.
- chemical , metabolism : Cytokines, Receptors, Antigen, T-Cell, alpha-beta.
- pathology : Encephalomyelitis, Autoimmune, Experimental.
- chemical , toxicity : Freund's Adjuvant, Myelin Proteolipid Protein, Peptide Fragments.
- Amino Acid Sequence, Animals, Disease Models, Animal, Female, Flow Cytometry, Mice, RNA, Messenger.
Abstract
Altered peptide ligands (APLs) have routinely been studied in clonal populations of Th cells that express a single T cell receptor (TCR), but results generated in this manner poorly predict the effects of APLs on polyclonal Th cells in vivo, contributing to the failure of phase II clinical trials of APLs in autoimmune diseases such as multiple sclerosis (MS). We have used a panel of APLs derived from an encephalitogenic epitope of myelin proteolipid protein to investigate the relationship between antigen cross-reactivity in a polyclonal environment, encephalitogenicity, and the capacity of an APL to provide protection against experimental autoimmune encephalomyelitis (EAE) in SJL mice. In general, polyclonal Th cell lines specific for encephalitogenic APLs cross-reacted with other encephalitogenic APLs, but not with non-encephalitogenic APLs, and vice versa. This, alongside analysis of TCR Vβ usage, suggested that encephalitogenic and non-encephalitogenic subgroups of APLs expand largely non-cross-reactive Th cell populations. As an exception to the rule, one non-encephalitogenic APL, L188, induced proliferation in polyclonal CD4(+) T cells specific for the native encephalitogen, with minimal induction of cytokine production. Co-immunization of L188 alongside the native encephalitogen slightly enhanced disease development. In contrast, another APL, A188, which induced IL-10 production without proliferation in CD4(+) T cells specific for the native encephalitogen, was able to protect against development of EAE in a dose-dependent fashion when co-immunized alongside the native encephalitogen. These results suggest that testing against polyclonal Th cell lines in vitro may be an effective strategy for distinguishing between potentially therapeutic and non-therapeutic APLs.
DOI: 10.1016/j.jneuroim.2017.03.011
PubMed: 28495132
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000B34
- to stream PubMed, to step Curation: 000B31
- to stream PubMed, to step Checkpoint: 000B31
- to stream Ncbi, to step Merge: 004799
- to stream Ncbi, to step Curation: 004799
- to stream Ncbi, to step Checkpoint: 004799
- to stream Main, to step Merge: 000571
- to stream Main, to step Curation: 000576
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Predicting the effects of potentially therapeutic modified peptides on polyclonal T cell populations in a mouse model of multiple sclerosis.</title><author><name sortKey="Sauer, Evan L" sort="Sauer, Evan L" uniqKey="Sauer E" first="Evan L" last="Sauer">Evan L. Sauer</name><affiliation wicri:level="1"><nlm:affiliation>The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Queensland, UQ Centre for Clinical Research, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Trifilieff, Elisabeth" sort="Trifilieff, Elisabeth" uniqKey="Trifilieff E" first="Elisabeth" last="Trifilieff">Elisabeth Trifilieff</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université de Strasbourg/CNRS, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université de Strasbourg/CNRS</wicri:regionArea><wicri:noRegion>Université de Strasbourg/CNRS</wicri:noRegion><wicri:noRegion>Université de Strasbourg/CNRS</wicri:noRegion></affiliation></author><author><name sortKey="Greer, Judith M" sort="Greer, Judith M" uniqKey="Greer J" first="Judith M" last="Greer">Judith M. Greer</name><affiliation wicri:level="1"><nlm:affiliation>The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. Electronic address: j.greer@uq.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Queensland, UQ Centre for Clinical Research, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28495132</idno><idno type="pmid">28495132</idno><idno type="doi">10.1016/j.jneuroim.2017.03.011</idno><idno type="wicri:Area/PubMed/Corpus">000B34</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000B34</idno><idno type="wicri:Area/PubMed/Curation">000B31</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000B31</idno><idno type="wicri:Area/PubMed/Checkpoint">000B31</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000B31</idno><idno type="wicri:Area/Ncbi/Merge">004799</idno><idno type="wicri:Area/Ncbi/Curation">004799</idno><idno type="wicri:Area/Ncbi/Checkpoint">004799</idno><idno type="wicri:Area/Main/Merge">000571</idno><idno type="wicri:Area/Main/Curation">000576</idno><idno type="wicri:Area/Main/Exploration">000576</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Predicting the effects of potentially therapeutic modified peptides on polyclonal T cell populations in a mouse model of multiple sclerosis.</title><author><name sortKey="Sauer, Evan L" sort="Sauer, Evan L" uniqKey="Sauer E" first="Evan L" last="Sauer">Evan L. Sauer</name><affiliation wicri:level="1"><nlm:affiliation>The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Queensland, UQ Centre for Clinical Research, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Trifilieff, Elisabeth" sort="Trifilieff, Elisabeth" uniqKey="Trifilieff E" first="Elisabeth" last="Trifilieff">Elisabeth Trifilieff</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université de Strasbourg/CNRS, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université de Strasbourg/CNRS</wicri:regionArea><wicri:noRegion>Université de Strasbourg/CNRS</wicri:noRegion><wicri:noRegion>Université de Strasbourg/CNRS</wicri:noRegion></affiliation></author><author><name sortKey="Greer, Judith M" sort="Greer, Judith M" uniqKey="Greer J" first="Judith M" last="Greer">Judith M. Greer</name><affiliation wicri:level="1"><nlm:affiliation>The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. Electronic address: j.greer@uq.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Queensland, UQ Centre for Clinical Research, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of neuroimmunology</title><idno type="eISSN">1872-8421</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antigen-Presenting Cells (drug effects)</term><term>Antigen-Presenting Cells (immunology)</term><term>Cell Proliferation (drug effects)</term><term>Cytokines (genetics)</term><term>Cytokines (metabolism)</term><term>Disease Models, Animal</term><term>Encephalomyelitis, Autoimmune, Experimental (chemically induced)</term><term>Encephalomyelitis, Autoimmune, Experimental (drug therapy)</term><term>Encephalomyelitis, Autoimmune, Experimental (immunology)</term><term>Encephalomyelitis, Autoimmune, Experimental (pathology)</term><term>Epitopes (chemistry)</term><term>Epitopes (immunology)</term><term>Female</term><term>Flow Cytometry</term><term>Freund's Adjuvant (toxicity)</term><term>Mice</term><term>Myelin Proteolipid Protein (chemistry)</term><term>Myelin Proteolipid Protein (genetics)</term><term>Myelin Proteolipid Protein (toxicity)</term><term>Peptide Fragments (chemistry)</term><term>Peptide Fragments (genetics)</term><term>Peptide Fragments (immunology)</term><term>Peptide Fragments (toxicity)</term><term>RNA, Messenger</term><term>Receptors, Antigen, T-Cell, alpha-beta (genetics)</term><term>Receptors, Antigen, T-Cell, alpha-beta (metabolism)</term><term>T-Lymphocytes (drug effects)</term><term>T-Lymphocytes (immunology)</term><term>Th1 Cells (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager</term><term>Adjuvant Freund (toxicité)</term><term>Animaux</term><term>Cellules présentatrices d'antigène ()</term><term>Cellules présentatrices d'antigène (immunologie)</term><term>Cytokines (génétique)</term><term>Cytokines (métabolisme)</term><term>Cytométrie en flux</term><term>Encéphalomyélite auto-immune expérimentale ()</term><term>Encéphalomyélite auto-immune expérimentale (anatomopathologie)</term><term>Encéphalomyélite auto-immune expérimentale (immunologie)</term><term>Encéphalomyélite auto-immune expérimentale (traitement médicamenteux)</term><term>Femelle</term><term>Fragments peptidiques ()</term><term>Fragments peptidiques (génétique)</term><term>Fragments peptidiques (immunologie)</term><term>Fragments peptidiques (toxicité)</term><term>Lymphocytes T ()</term><term>Lymphocytes T (immunologie)</term><term>Lymphocytes auxiliaires Th1 ()</term><term>Modèles animaux de maladie humaine</term><term>Prolifération cellulaire ()</term><term>Protéine protéolipidique myéline ()</term><term>Protéine protéolipidique myéline (génétique)</term><term>Protéine protéolipidique myéline (toxicité)</term><term>Récepteur lymphocytaire T antigène, alpha-bêta (génétique)</term><term>Récepteur lymphocytaire T antigène, alpha-bêta (métabolisme)</term><term>Souris</term><term>Séquence d'acides aminés</term><term>Épitopes ()</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term><term>Myelin Proteolipid Protein</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cytokines</term><term>Myelin Proteolipid Protein</term><term>Peptide Fragments</term><term>Receptors, Antigen, T-Cell, alpha-beta</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Encéphalomyélite auto-immune expérimentale</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Encephalomyelitis, Autoimmune, Experimental</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Antigen-Presenting Cells</term><term>Cell Proliferation</term><term>T-Lymphocytes</term><term>Th1 Cells</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Encephalomyelitis, Autoimmune, Experimental</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cytokines</term><term>Fragments peptidiques</term><term>Protéine protéolipidique myéline</term><term>Récepteur lymphocytaire T antigène, alpha-bêta</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules présentatrices d'antigène</term><term>Encéphalomyélite auto-immune expérimentale</term><term>Fragments peptidiques</term><term>Lymphocytes T</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Antigen-Presenting Cells</term><term>Encephalomyelitis, Autoimmune, Experimental</term><term>Epitopes</term><term>Peptide Fragments</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Receptors, Antigen, T-Cell, alpha-beta</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cytokines</term><term>Récepteur lymphocytaire T antigène, alpha-bêta</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Encephalomyelitis, Autoimmune, Experimental</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Freund's Adjuvant</term><term>Myelin Proteolipid Protein</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Adjuvant Freund</term><term>Fragments peptidiques</term><term>Protéine protéolipidique myéline</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Encéphalomyélite auto-immune expérimentale</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Flow Cytometry</term><term>Mice</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN messager</term><term>Animaux</term><term>Cellules présentatrices d'antigène</term><term>Cytométrie en flux</term><term>Encéphalomyélite auto-immune expérimentale</term><term>Femelle</term><term>Fragments peptidiques</term><term>Lymphocytes T</term><term>Lymphocytes auxiliaires Th1</term><term>Modèles animaux de maladie humaine</term><term>Prolifération cellulaire</term><term>Protéine protéolipidique myéline</term><term>Souris</term><term>Séquence d'acides aminés</term><term>Épitopes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Altered peptide ligands (APLs) have routinely been studied in clonal populations of Th cells that express a single T cell receptor (TCR), but results generated in this manner poorly predict the effects of APLs on polyclonal Th cells in vivo, contributing to the failure of phase II clinical trials of APLs in autoimmune diseases such as multiple sclerosis (MS). We have used a panel of APLs derived from an encephalitogenic epitope of myelin proteolipid protein to investigate the relationship between antigen cross-reactivity in a polyclonal environment, encephalitogenicity, and the capacity of an APL to provide protection against experimental autoimmune encephalomyelitis (EAE) in SJL mice. In general, polyclonal Th cell lines specific for encephalitogenic APLs cross-reacted with other encephalitogenic APLs, but not with non-encephalitogenic APLs, and vice versa. This, alongside analysis of TCR Vβ usage, suggested that encephalitogenic and non-encephalitogenic subgroups of APLs expand largely non-cross-reactive Th cell populations. As an exception to the rule, one non-encephalitogenic APL, L188, induced proliferation in polyclonal CD4(+) T cells specific for the native encephalitogen, with minimal induction of cytokine production. Co-immunization of L188 alongside the native encephalitogen slightly enhanced disease development. In contrast, another APL, A188, which induced IL-10 production without proliferation in CD4(+) T cells specific for the native encephalitogen, was able to protect against development of EAE in a dose-dependent fashion when co-immunized alongside the native encephalitogen. These results suggest that testing against polyclonal Th cell lines in vitro may be an effective strategy for distinguishing between potentially therapeutic and non-therapeutic APLs.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Sauer, Evan L" sort="Sauer, Evan L" uniqKey="Sauer E" first="Evan L" last="Sauer">Evan L. Sauer</name></noRegion><name sortKey="Greer, Judith M" sort="Greer, Judith M" uniqKey="Greer J" first="Judith M" last="Greer">Judith M. Greer</name></country><country name="France"><noRegion><name sortKey="Trifilieff, Elisabeth" sort="Trifilieff, Elisabeth" uniqKey="Trifilieff E" first="Elisabeth" last="Trifilieff">Elisabeth Trifilieff</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000576 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000576 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:28495132
|texte= Predicting the effects of potentially therapeutic modified peptides on polyclonal T cell populations in a mouse model of multiple sclerosis.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:28495132" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |