ANALYSIS OF HUMAN IL-2/IL-2 RECEPTOR β CHAIN INTERACTIONS: MONOCLONAL ANTIBODY H2-8 AND NEW IL-2 MUTANTS DEFINE THE CRITICAL ROLE OF α HELIX-A OF IL-2
Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits (IL-2Rα, IL-2Rβ and IL-2Rγ). IL-2Rβ plays a critical role in signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20,...
Gespeichert in:
| Veröffentlicht in: | Cytokine (Philadelphia, Pa.) Pa.), 1997-07, Vol.9 (7), p.488-498 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 498 |
|---|---|
| container_issue | 7 |
| container_start_page | 488 |
| container_title | Cytokine (Philadelphia, Pa.) |
| container_volume | 9 |
| creator | Eckenberg, Ralph Xu, Di Moreau, Jean-Louis Bossus, Marc Mazié, Jean-Claude Tartar, André Liu, Xin Yuan Alzari, Pedro M. Bertoglio, Jacques Thèze, Jacques |
| description | Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits (IL-2Rα, IL-2Rβ and IL-2Rγ). IL-2Rβ plays a critical role in signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20, at the exposed interface between α-helices A and C. Muteins at position 17 and 20 are not recognized by mAb H2-8. mAb H2-8 specifically inhibits the IL-2 proliferation of TS1β cells which are dependent on the expression of human Il-2Rβ chain for IL-2 proliferation. Substitution at internal position Leu17 demonstrated that this position is essential for IL-2 binding and IL-2 bioactivity. New IL-2 mutants at position Asp20 have been analysed. Substitutions Asp→Asn, Asp→Lys, Asp→Leu, show a correlation between diminished affinity for IL-2 receptor and reduced bioactivity measured on TS1β cells. Mutein Asp→Arg lose affinity for IL-2R and bioactivity simultaneously. Furthermore, during the course of the study we have found that mutein Asp20→Leu is an IL-2 antagonist. The biological effects of mAb H2-8 and the properties of new mutants at positions 17 and 20 demonstrate that this region of α helix-A is involved in IL-2–IL-2Rβ interactions. |
| doi_str_mv | 10.1006/cyto.1996.0192 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_pasteur_03136632v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1043466696901921</els_id><sourcerecordid>S1043466696901921</sourcerecordid><originalsourceid>FETCH-LOGICAL-c377t-2ca4c8aafacd54bcd284cf68f8b3ff5a3923b8ce3a85e520d43dabd52af84a643</originalsourceid><addsrcrecordid>eNp1kU9u1DAYxS0EKqWwZYfkC3jqP4nHYRcyHmIpE6NMRtCV5TiOCGqZUTKt1JtwDXqQnqk2U3XHxvan9_2e9fQA-EjwgmDML939cb8gWcYXmGT0FTgnOOMIY8pex3fCUMI5fwvezfMvjHHGlsszcJZRthSEnIM_eZ1XV1u1hXoNy90mr6GqEL2MB2xkIb-1uoGPD7AocxW0upVNXrRK19vPcKNrXVQ6OMC8btUXvbqCJUUiTCtYy-__rOBm1wZ1C1dyrWoJ21LColGtKgLW6ErGnx__wlJW6gfK4xSx9-DNYK9n_-H5vgC7tWyLElX6a0SRC0mOiDqbOGHtYF2fJp3rqUjcwMUgOjYMqWUhaSecZ1akPqW4T1hvuz6ldhCJ5Qm7AOjk-9Nem8M03tjp3uztaMq8Mgc7H_3tZDAjjHNG70jYX5z23bSf58kPLxDBJjZiYiMmNmJiIwH4dAIOt92N71_WnysIujjpPqS8G_1kZjf638734-Td0fT78X_WT57Mj4c</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>ANALYSIS OF HUMAN IL-2/IL-2 RECEPTOR β CHAIN INTERACTIONS: MONOCLONAL ANTIBODY H2-8 AND NEW IL-2 MUTANTS DEFINE THE CRITICAL ROLE OF α HELIX-A OF IL-2</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Eckenberg, Ralph ; Xu, Di ; Moreau, Jean-Louis ; Bossus, Marc ; Mazié, Jean-Claude ; Tartar, André ; Liu, Xin Yuan ; Alzari, Pedro M. ; Bertoglio, Jacques ; Thèze, Jacques</creator><creatorcontrib>Eckenberg, Ralph ; Xu, Di ; Moreau, Jean-Louis ; Bossus, Marc ; Mazié, Jean-Claude ; Tartar, André ; Liu, Xin Yuan ; Alzari, Pedro M. ; Bertoglio, Jacques ; Thèze, Jacques</creatorcontrib><description>Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits (IL-2Rα, IL-2Rβ and IL-2Rγ). IL-2Rβ plays a critical role in signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20, at the exposed interface between α-helices A and C. Muteins at position 17 and 20 are not recognized by mAb H2-8. mAb H2-8 specifically inhibits the IL-2 proliferation of TS1β cells which are dependent on the expression of human Il-2Rβ chain for IL-2 proliferation. Substitution at internal position Leu17 demonstrated that this position is essential for IL-2 binding and IL-2 bioactivity. New IL-2 mutants at position Asp20 have been analysed. Substitutions Asp→Asn, Asp→Lys, Asp→Leu, show a correlation between diminished affinity for IL-2 receptor and reduced bioactivity measured on TS1β cells. Mutein Asp→Arg lose affinity for IL-2R and bioactivity simultaneously. Furthermore, during the course of the study we have found that mutein Asp20→Leu is an IL-2 antagonist. The biological effects of mAb H2-8 and the properties of new mutants at positions 17 and 20 demonstrate that this region of α helix-A is involved in IL-2–IL-2Rβ interactions.</description><identifier>ISSN: 1043-4666</identifier><identifier>EISSN: 1096-0023</identifier><identifier>DOI: 10.1006/cyto.1996.0192</identifier><identifier>PMID: 9237811</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antibodies, Monoclonal ; Aspartic Acid ; Aspartic Acid - metabolism ; Base Sequence ; Binding Sites ; Biochemistry, Molecular Biology ; Bioinformatics ; Biological Physics ; Cellular Biology ; Chemical Sciences ; Computer Science ; Cristallography ; DNA ; Female ; function ; Humans ; IL-2 muteins ; IL-2 receptors ; IL-2 structure ; Interleukin-2 ; Interleukin-2 - chemistry ; Interleukin-2 - genetics ; Interleukin-2 - metabolism ; Leucine ; Leucine - metabolism ; Life Sciences ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Mutagenesis ; Physics ; Protein Binding ; Protein Structure, Secondary ; Receptors, Interleukin-2 ; Receptors, Interleukin-2 - metabolism ; Structural Biology ; Structure-Activity Relationship</subject><ispartof>Cytokine (Philadelphia, Pa.), 1997-07, Vol.9 (7), p.488-498</ispartof><rights>1997 Academic Press</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-2ca4c8aafacd54bcd284cf68f8b3ff5a3923b8ce3a85e520d43dabd52af84a643</citedby><orcidid>0000-0002-4233-1903</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/cyto.1996.0192$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9237811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-03136632$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Eckenberg, Ralph</creatorcontrib><creatorcontrib>Xu, Di</creatorcontrib><creatorcontrib>Moreau, Jean-Louis</creatorcontrib><creatorcontrib>Bossus, Marc</creatorcontrib><creatorcontrib>Mazié, Jean-Claude</creatorcontrib><creatorcontrib>Tartar, André</creatorcontrib><creatorcontrib>Liu, Xin Yuan</creatorcontrib><creatorcontrib>Alzari, Pedro M.</creatorcontrib><creatorcontrib>Bertoglio, Jacques</creatorcontrib><creatorcontrib>Thèze, Jacques</creatorcontrib><title>ANALYSIS OF HUMAN IL-2/IL-2 RECEPTOR β CHAIN INTERACTIONS: MONOCLONAL ANTIBODY H2-8 AND NEW IL-2 MUTANTS DEFINE THE CRITICAL ROLE OF α HELIX-A OF IL-2</title><title>Cytokine (Philadelphia, Pa.)</title><addtitle>Cytokine</addtitle><description>Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits (IL-2Rα, IL-2Rβ and IL-2Rγ). IL-2Rβ plays a critical role in signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20, at the exposed interface between α-helices A and C. Muteins at position 17 and 20 are not recognized by mAb H2-8. mAb H2-8 specifically inhibits the IL-2 proliferation of TS1β cells which are dependent on the expression of human Il-2Rβ chain for IL-2 proliferation. Substitution at internal position Leu17 demonstrated that this position is essential for IL-2 binding and IL-2 bioactivity. New IL-2 mutants at position Asp20 have been analysed. Substitutions Asp→Asn, Asp→Lys, Asp→Leu, show a correlation between diminished affinity for IL-2 receptor and reduced bioactivity measured on TS1β cells. Mutein Asp→Arg lose affinity for IL-2R and bioactivity simultaneously. Furthermore, during the course of the study we have found that mutein Asp20→Leu is an IL-2 antagonist. The biological effects of mAb H2-8 and the properties of new mutants at positions 17 and 20 demonstrate that this region of α helix-A is involved in IL-2–IL-2Rβ interactions.</description><subject>Animals</subject><subject>Antibodies, Monoclonal</subject><subject>Aspartic Acid</subject><subject>Aspartic Acid - metabolism</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Biochemistry, Molecular Biology</subject><subject>Bioinformatics</subject><subject>Biological Physics</subject><subject>Cellular Biology</subject><subject>Chemical Sciences</subject><subject>Computer Science</subject><subject>Cristallography</subject><subject>DNA</subject><subject>Female</subject><subject>function</subject><subject>Humans</subject><subject>IL-2 muteins</subject><subject>IL-2 receptors</subject><subject>IL-2 structure</subject><subject>Interleukin-2</subject><subject>Interleukin-2 - chemistry</subject><subject>Interleukin-2 - genetics</subject><subject>Interleukin-2 - metabolism</subject><subject>Leucine</subject><subject>Leucine - metabolism</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis</subject><subject>Physics</subject><subject>Protein Binding</subject><subject>Protein Structure, Secondary</subject><subject>Receptors, Interleukin-2</subject><subject>Receptors, Interleukin-2 - metabolism</subject><subject>Structural Biology</subject><subject>Structure-Activity Relationship</subject><issn>1043-4666</issn><issn>1096-0023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9u1DAYxS0EKqWwZYfkC3jqP4nHYRcyHmIpE6NMRtCV5TiOCGqZUTKt1JtwDXqQnqk2U3XHxvan9_2e9fQA-EjwgmDML939cb8gWcYXmGT0FTgnOOMIY8pex3fCUMI5fwvezfMvjHHGlsszcJZRthSEnIM_eZ1XV1u1hXoNy90mr6GqEL2MB2xkIb-1uoGPD7AocxW0upVNXrRK19vPcKNrXVQ6OMC8btUXvbqCJUUiTCtYy-__rOBm1wZ1C1dyrWoJ21LColGtKgLW6ErGnx__wlJW6gfK4xSx9-DNYK9n_-H5vgC7tWyLElX6a0SRC0mOiDqbOGHtYF2fJp3rqUjcwMUgOjYMqWUhaSecZ1akPqW4T1hvuz6ldhCJ5Qm7AOjk-9Nem8M03tjp3uztaMq8Mgc7H_3tZDAjjHNG70jYX5z23bSf58kPLxDBJjZiYiMmNmJiIwH4dAIOt92N71_WnysIujjpPqS8G_1kZjf638734-Td0fT78X_WT57Mj4c</recordid><startdate>19970701</startdate><enddate>19970701</enddate><creator>Eckenberg, Ralph</creator><creator>Xu, Di</creator><creator>Moreau, Jean-Louis</creator><creator>Bossus, Marc</creator><creator>Mazié, Jean-Claude</creator><creator>Tartar, André</creator><creator>Liu, Xin Yuan</creator><creator>Alzari, Pedro M.</creator><creator>Bertoglio, Jacques</creator><creator>Thèze, Jacques</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-4233-1903</orcidid></search><sort><creationdate>19970701</creationdate><title>ANALYSIS OF HUMAN IL-2/IL-2 RECEPTOR β CHAIN INTERACTIONS: MONOCLONAL ANTIBODY H2-8 AND NEW IL-2 MUTANTS DEFINE THE CRITICAL ROLE OF α HELIX-A OF IL-2</title><author>Eckenberg, Ralph ; Xu, Di ; Moreau, Jean-Louis ; Bossus, Marc ; Mazié, Jean-Claude ; Tartar, André ; Liu, Xin Yuan ; Alzari, Pedro M. ; Bertoglio, Jacques ; Thèze, Jacques</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-2ca4c8aafacd54bcd284cf68f8b3ff5a3923b8ce3a85e520d43dabd52af84a643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal</topic><topic>Aspartic Acid</topic><topic>Aspartic Acid - metabolism</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Biochemistry, Molecular Biology</topic><topic>Bioinformatics</topic><topic>Biological Physics</topic><topic>Cellular Biology</topic><topic>Chemical Sciences</topic><topic>Computer Science</topic><topic>Cristallography</topic><topic>DNA</topic><topic>Female</topic><topic>function</topic><topic>Humans</topic><topic>IL-2 muteins</topic><topic>IL-2 receptors</topic><topic>IL-2 structure</topic><topic>Interleukin-2</topic><topic>Interleukin-2 - chemistry</topic><topic>Interleukin-2 - genetics</topic><topic>Interleukin-2 - metabolism</topic><topic>Leucine</topic><topic>Leucine - metabolism</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis</topic><topic>Physics</topic><topic>Protein Binding</topic><topic>Protein Structure, Secondary</topic><topic>Receptors, Interleukin-2</topic><topic>Receptors, Interleukin-2 - metabolism</topic><topic>Structural Biology</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eckenberg, Ralph</creatorcontrib><creatorcontrib>Xu, Di</creatorcontrib><creatorcontrib>Moreau, Jean-Louis</creatorcontrib><creatorcontrib>Bossus, Marc</creatorcontrib><creatorcontrib>Mazié, Jean-Claude</creatorcontrib><creatorcontrib>Tartar, André</creatorcontrib><creatorcontrib>Liu, Xin Yuan</creatorcontrib><creatorcontrib>Alzari, Pedro M.</creatorcontrib><creatorcontrib>Bertoglio, Jacques</creatorcontrib><creatorcontrib>Thèze, Jacques</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Cytokine (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eckenberg, Ralph</au><au>Xu, Di</au><au>Moreau, Jean-Louis</au><au>Bossus, Marc</au><au>Mazié, Jean-Claude</au><au>Tartar, André</au><au>Liu, Xin Yuan</au><au>Alzari, Pedro M.</au><au>Bertoglio, Jacques</au><au>Thèze, Jacques</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ANALYSIS OF HUMAN IL-2/IL-2 RECEPTOR β CHAIN INTERACTIONS: MONOCLONAL ANTIBODY H2-8 AND NEW IL-2 MUTANTS DEFINE THE CRITICAL ROLE OF α HELIX-A OF IL-2</atitle><jtitle>Cytokine (Philadelphia, Pa.)</jtitle><addtitle>Cytokine</addtitle><date>1997-07-01</date><risdate>1997</risdate><volume>9</volume><issue>7</issue><spage>488</spage><epage>498</epage><pages>488-498</pages><issn>1043-4666</issn><eissn>1096-0023</eissn><abstract>Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits (IL-2Rα, IL-2Rβ and IL-2Rγ). IL-2Rβ plays a critical role in signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20, at the exposed interface between α-helices A and C. Muteins at position 17 and 20 are not recognized by mAb H2-8. mAb H2-8 specifically inhibits the IL-2 proliferation of TS1β cells which are dependent on the expression of human Il-2Rβ chain for IL-2 proliferation. Substitution at internal position Leu17 demonstrated that this position is essential for IL-2 binding and IL-2 bioactivity. New IL-2 mutants at position Asp20 have been analysed. Substitutions Asp→Asn, Asp→Lys, Asp→Leu, show a correlation between diminished affinity for IL-2 receptor and reduced bioactivity measured on TS1β cells. Mutein Asp→Arg lose affinity for IL-2R and bioactivity simultaneously. Furthermore, during the course of the study we have found that mutein Asp20→Leu is an IL-2 antagonist. The biological effects of mAb H2-8 and the properties of new mutants at positions 17 and 20 demonstrate that this region of α helix-A is involved in IL-2–IL-2Rβ interactions.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>9237811</pmid><doi>10.1006/cyto.1996.0192</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4233-1903</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1043-4666 |
| ispartof | Cytokine (Philadelphia, Pa.), 1997-07, Vol.9 (7), p.488-498 |
| issn | 1043-4666 1096-0023 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_pasteur_03136632v1 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Antibodies, Monoclonal Aspartic Acid Aspartic Acid - metabolism Base Sequence Binding Sites Biochemistry, Molecular Biology Bioinformatics Biological Physics Cellular Biology Chemical Sciences Computer Science Cristallography DNA Female function Humans IL-2 muteins IL-2 receptors IL-2 structure Interleukin-2 Interleukin-2 - chemistry Interleukin-2 - genetics Interleukin-2 - metabolism Leucine Leucine - metabolism Life Sciences Mice Mice, Inbred BALB C Molecular Sequence Data Mutagenesis Physics Protein Binding Protein Structure, Secondary Receptors, Interleukin-2 Receptors, Interleukin-2 - metabolism Structural Biology Structure-Activity Relationship |
| title | ANALYSIS OF HUMAN IL-2/IL-2 RECEPTOR β CHAIN INTERACTIONS: MONOCLONAL ANTIBODY H2-8 AND NEW IL-2 MUTANTS DEFINE THE CRITICAL ROLE OF α HELIX-A OF IL-2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T02%3A59%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ANALYSIS%20OF%20HUMAN%20IL-2/IL-2%20RECEPTOR%20%CE%B2%20CHAIN%20INTERACTIONS:%20MONOCLONAL%20ANTIBODY%20H2-8%20AND%20NEW%20IL-2%20MUTANTS%20DEFINE%20THE%20CRITICAL%20ROLE%20OF%20%CE%B1%20HELIX-A%20OF%20IL-2&rft.jtitle=Cytokine%20(Philadelphia,%20Pa.)&rft.au=Eckenberg,%20Ralph&rft.date=1997-07-01&rft.volume=9&rft.issue=7&rft.spage=488&rft.epage=498&rft.pages=488-498&rft.issn=1043-4666&rft.eissn=1096-0023&rft_id=info:doi/10.1006/cyto.1996.0192&rft_dat=%3Celsevier_hal_p%3ES1043466696901921%3C/elsevier_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/9237811&rft_els_id=S1043466696901921&rfr_iscdi=true |