The Diversity of Antigen-Specific TCR Repertoires Reflects the Relative Complexity of Epitopes Recognized
Identifieur interne : 000303 ( France/Analysis ); précédent : 000302; suivant : 000304The Diversity of Antigen-Specific TCR Repertoires Reflects the Relative Complexity of Epitopes Recognized
Auteurs : Janet L. Maryanski [Suisse] ; Jean-Laurent Casanova [Suisse] ; Kirsten Falk [États-Unis] ; Hélène Gournier [France] ; Christian Jaulin [France] ; Philippe Kourilsky [France] ; François A. Lemonnier [France] ; Roland Lüthy [Suisse] ; Hans-Georg Rammensee [Allemagne] ; Olaf Rötzschke [États-Unis] ; Catherine Servis [Suisse] ; José Alejandro L Pez [Suisse]Source :
- Human Immunology [ 0198-8859 ] ; 1997.
English descriptors
- KwdEn :
- Teeft :
- Acid extraction, American society, Amino acid, Antigen recognition, Antigenic, Antigenic material, Antigenic peptide, Antigenic peptides, Antigenic variants, Binding motif, Casanova, Casanova maryanski, Casanova romero, Cell eluates, Cell epitopes, Cell receptor, Cell receptors, Cell recognition, Cell response, Cells transfected, Cerottini corradin, Clone, Competitor activity, Corradin, Cytolytic, Cytotoxic, Different tcrs, Distinct epitopes, Ecole normale superieur, Epitope, Flow rate, Functional studies, Gene segment, Gene segments, Histocompatibility, Hplc, Hplc fractions, Human gene, Human immunology, Immune response, Immunol, Individual fractions, Influenza virus hemagglutinin, Ligand, Lymphocyte, Lyon cedex, Major histocompatibility, Maryanski, Maximal lysis, Molecular model, Molecular weight, Molecule, Molecules immunoprecipitated, Monoclonal antibody, Mutant, Mutant molecules, Natural ligands, Natural peptide ligands, Other complexes, Other positions, Pbcs, Pbcs peptide, Peptide, Peptide ligands, Peptide recognition, Peptide residues, Peptide sequences, Proc natl acad, Receptor, Relative antigenic activity, Relative competitor activity, Repertoire, Residue, Reversephase hplc, Romero, Side chains, Similar binding motif, Similar tcrs, Single pbcs peptides, Specific activity, Spontaneous release, Synthetic peptide, Synthetic peptides, Target cells, Tcrs, Transfectants, Transfected, Transfected cells, Tyrosine kinase jak1.
Abstract
Abstract: Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 Kd. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252–260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170–179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant H-2 Kd molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/Kd complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.
Url:
DOI: 10.1016/S0198-8859(97)00082-7
Affiliations:
- Allemagne, France, Suisse, États-Unis
- Bade-Wurtemberg, Canton de Vaud, District de Tübingen, Massachusetts, Île-de-France
- Cambridge (Massachusetts), Lausanne, Paris, Tübingen
- Université Harvard, Université de Lausanne
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Maryanski</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Ludwig Institute for Cancer Research, Lausanne Branch (J.L.M., J.-L.C., J.A.L.), CH-1066 Epalinges</wicri:regionArea><wicri:noRegion>CH-1066 Epalinges</wicri:noRegion></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Ludwig Institute for Cancer Research, Lausanne Branch (J.L.M., J.-L.C., J.A.L.), CH-1066 Epalinges</wicri:regionArea><wicri:noRegion>CH-1066 Epalinges</wicri:noRegion></affiliation></author><author><name sortKey="Falk, Kirsten" sort="Falk, Kirsten" uniqKey="Falk K" first="Kirsten" last="Falk">Kirsten Falk</name><affiliation wicri:level="4"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Harvard University (K.F., O.R.), Cambridge, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Gournier, Helene" sort="Gournier, Helene" uniqKey="Gournier H" first="Hélène" last="Gournier">Hélène Gournier</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Institut Pasteur (H.G., C.J., P.K., F.A.L.), Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Jaulin, Christian" sort="Jaulin, Christian" uniqKey="Jaulin C" first="Christian" last="Jaulin">Christian Jaulin</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Institut Pasteur (H.G., C.J., P.K., F.A.L.), Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kourilsky, Philippe" sort="Kourilsky, Philippe" uniqKey="Kourilsky P" first="Philippe" last="Kourilsky">Philippe Kourilsky</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Institut Pasteur (H.G., C.J., P.K., F.A.L.), Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lemonnier, Francois A" sort="Lemonnier, Francois A" uniqKey="Lemonnier F" first="François A" last="Lemonnier">François A. Lemonnier</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Institut Pasteur (H.G., C.J., P.K., F.A.L.), Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Luthy, Roland" sort="Luthy, Roland" uniqKey="Luthy R" first="Roland" last="Lüthy">Roland Lüthy</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Swiss Institute for Experimental Cancer Research (R.L.), Epalinges</wicri:regionArea><wicri:noRegion>Epalinges</wicri:noRegion></affiliation></author><author><name sortKey="Rammensee, Hans Georg" sort="Rammensee, Hans Georg" uniqKey="Rammensee H" first="Hans-Georg" last="Rammensee">Hans-Georg Rammensee</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Interfakultäres Institut für Zellbiologie, Abteilung Immunologie, Universität Tübingen (H.-G.R.), Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Rotzschke, Olaf" sort="Rotzschke, Olaf" uniqKey="Rotzschke O" first="Olaf" last="Rötzschke">Olaf Rötzschke</name><affiliation wicri:level="4"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Harvard University (K.F., O.R.), Cambridge, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Servis, Catherine" sort="Servis, Catherine" uniqKey="Servis C" first="Catherine" last="Servis">Catherine Servis</name><affiliation wicri:level="4"><country xml:lang="fr">Suisse</country><wicri:regionArea>Institut de Biochimie, Université de Lausanne (C.S., J.A.L.), Epalinges</wicri:regionArea><orgName type="university">Université de Lausanne</orgName><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="L Pez, Jose Alejandro" sort="L Pez, Jose Alejandro" uniqKey="L Pez J" first="José Alejandro" last="L Pez">José Alejandro L Pez</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Ludwig Institute for Cancer Research, Lausanne Branch (J.L.M., J.-L.C., J.A.L.), CH-1066 Epalinges</wicri:regionArea><wicri:noRegion>CH-1066 Epalinges</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Immunology</title><title level="j" type="abbrev">HIM</title><idno type="ISSN">0198-8859</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1997">1997</date><biblScope unit="volume">54</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="117">117</biblScope><biblScope unit="page" to="128">128</biblScope></imprint><idno type="ISSN">0198-8859</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0198-8859</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CTL</term><term>EBNA</term><term>MALDI/MS</term><term>MHC</term><term>NP</term><term>PbCS</term><term>TCR</term><term>pM50</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Acid extraction</term><term>American society</term><term>Amino acid</term><term>Antigen recognition</term><term>Antigenic</term><term>Antigenic material</term><term>Antigenic peptide</term><term>Antigenic peptides</term><term>Antigenic variants</term><term>Binding motif</term><term>Casanova</term><term>Casanova maryanski</term><term>Casanova romero</term><term>Cell eluates</term><term>Cell epitopes</term><term>Cell receptor</term><term>Cell receptors</term><term>Cell recognition</term><term>Cell response</term><term>Cells transfected</term><term>Cerottini corradin</term><term>Clone</term><term>Competitor activity</term><term>Corradin</term><term>Cytolytic</term><term>Cytotoxic</term><term>Different tcrs</term><term>Distinct epitopes</term><term>Ecole normale superieur</term><term>Epitope</term><term>Flow rate</term><term>Functional studies</term><term>Gene segment</term><term>Gene segments</term><term>Histocompatibility</term><term>Hplc</term><term>Hplc fractions</term><term>Human gene</term><term>Human immunology</term><term>Immune response</term><term>Immunol</term><term>Individual fractions</term><term>Influenza virus hemagglutinin</term><term>Ligand</term><term>Lymphocyte</term><term>Lyon cedex</term><term>Major histocompatibility</term><term>Maryanski</term><term>Maximal lysis</term><term>Molecular model</term><term>Molecular weight</term><term>Molecule</term><term>Molecules immunoprecipitated</term><term>Monoclonal antibody</term><term>Mutant</term><term>Mutant molecules</term><term>Natural ligands</term><term>Natural peptide ligands</term><term>Other complexes</term><term>Other positions</term><term>Pbcs</term><term>Pbcs peptide</term><term>Peptide</term><term>Peptide ligands</term><term>Peptide recognition</term><term>Peptide residues</term><term>Peptide sequences</term><term>Proc natl acad</term><term>Receptor</term><term>Relative antigenic activity</term><term>Relative competitor activity</term><term>Repertoire</term><term>Residue</term><term>Reversephase hplc</term><term>Romero</term><term>Side chains</term><term>Similar binding motif</term><term>Similar tcrs</term><term>Single pbcs peptides</term><term>Specific activity</term><term>Spontaneous release</term><term>Synthetic peptide</term><term>Synthetic peptides</term><term>Target cells</term><term>Tcrs</term><term>Transfectants</term><term>Transfected</term><term>Transfected cells</term><term>Tyrosine kinase jak1</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 Kd. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252–260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170–179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant H-2 Kd molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/Kd complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Suisse</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>Canton de Vaud</li><li>District de Tübingen</li><li>Massachusetts</li><li>Île-de-France</li></region><settlement><li>Cambridge (Massachusetts)</li><li>Lausanne</li><li>Paris</li><li>Tübingen</li></settlement><orgName><li>Université Harvard</li><li>Université de Lausanne</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Maryanski, Janet L" sort="Maryanski, Janet L" uniqKey="Maryanski J" first="Janet L" last="Maryanski">Janet L. Maryanski</name></noRegion><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><name sortKey="L Pez, Jose Alejandro" sort="L Pez, Jose Alejandro" uniqKey="L Pez J" first="José Alejandro" last="L Pez">José Alejandro L Pez</name><name sortKey="Luthy, Roland" sort="Luthy, Roland" uniqKey="Luthy R" first="Roland" last="Lüthy">Roland Lüthy</name><name sortKey="Servis, Catherine" sort="Servis, Catherine" uniqKey="Servis C" first="Catherine" last="Servis">Catherine Servis</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Falk, Kirsten" sort="Falk, Kirsten" uniqKey="Falk K" first="Kirsten" last="Falk">Kirsten Falk</name></region><name sortKey="Rotzschke, Olaf" sort="Rotzschke, Olaf" uniqKey="Rotzschke O" first="Olaf" last="Rötzschke">Olaf Rötzschke</name></country><country name="France"><region name="Île-de-France"><name sortKey="Gournier, Helene" sort="Gournier, Helene" uniqKey="Gournier H" first="Hélène" last="Gournier">Hélène Gournier</name></region><name sortKey="Jaulin, Christian" sort="Jaulin, Christian" uniqKey="Jaulin C" first="Christian" last="Jaulin">Christian Jaulin</name><name sortKey="Kourilsky, Philippe" sort="Kourilsky, Philippe" uniqKey="Kourilsky P" first="Philippe" last="Kourilsky">Philippe Kourilsky</name><name sortKey="Lemonnier, Francois A" sort="Lemonnier, Francois A" uniqKey="Lemonnier F" first="François A" last="Lemonnier">François A. Lemonnier</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Rammensee, Hans Georg" sort="Rammensee, Hans Georg" uniqKey="Rammensee H" first="Hans-Georg" last="Rammensee">Hans-Georg Rammensee</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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