Proteolytic Cleavage of a Self-Antigen Following Xenobiotic-Induced Cell Death Produces a Fragment with Novel Immunogenic Properties
The heavy metal mercury elicits a genetically restricted autoantibody response in mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent feature of mercury-induced cell death was the generation...
Gespeichert in:
Veröffentlicht in: | The Journal of immunology (1950) 2000-08, Vol.165 (4), p.2263-2270 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2270 |
---|---|
container_issue | 4 |
container_start_page | 2263 |
container_title | The Journal of immunology (1950) |
container_volume | 165 |
creator | Pollard, K. Michael Pearson, Deborah L Bluthner, Martin Tan, Eng M |
description | The heavy metal mercury elicits a genetically restricted autoantibody response in mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent feature of mercury-induced cell death was the generation of a 19-kDa fragment of fibrillarin that was not found following apoptotic or nonapoptotic cell death induced by stimuli other than mercury. Proteolysis of fibrillarin lacking cysteines, and therefore unable to bind mercury, also produced the 19-kDa fragment, suggesting that a mercury-fibrillarin interaction was not necessary for the unique cleavage pattern of this self-Ag. In contrast to immunization with full-length fibrillarin, the 19-kDa fragment produced anti-fibrillarin Abs with some of the properties of the HgCl2-induced anti-fibrillarin response. We propose that cell death following exposure to an autoimmunity-inducing xenobiotic can lead to the generation of novel protein fragments that may serve as sources of antigenic determinants for self-reactive T lymphocytes. |
doi_str_mv | 10.4049/jimmunol.165.4.2263 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17563735</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17563735</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-fc3c5b03d39b8a9bdea57f4cbbf3d7069065a155f24604fb09a60e94a4e391363</originalsourceid><addsrcrecordid>eNpNkM1u1DAURi1ERYfCEyAhr2CV4Tr-CV5WUwZGqmglQGJnOclNxpUTD3bSqPs-OB6mSF1Zss_3-d5DyDsGawFCf7pzwzCPwa-ZkmuxLkvFX5AVkxIKpUC9JCuAsixYpapz8jqlOwBQUIpX5JyBLiVnckUeb2OYMPiHyTV049He2x5p6KilP9B3xeU4uR5Hug3eh8WNPf2NY6hdyHyxG9u5wZZu0Ht6hXba01x3vEs5v422H3Cc6OLyw_dwj57u_o2cC_NvGT1gnBymN-Sssz7h26fzgvzafvm5-VZc33zdbS6vi0aAnoqu4Y2sgbdc15-trlu0supEU9cdbytQGpS0ef-uFApEV4O2ClALK5BrxhW_IB9OvYcY_syYJjO41OTh7YhhToZVUvGKywzyE9jEkFLEzhyiG2x8MAzMUb75L99k-UaYo_ycev9UP9cDts8yJ9sZ-HgC9q7fLy6iSYP1PuPMLMvyrOovt4iSHQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17563735</pqid></control><display><type>article</type><title>Proteolytic Cleavage of a Self-Antigen Following Xenobiotic-Induced Cell Death Produces a Fragment with Novel Immunogenic Properties</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Pollard, K. Michael ; Pearson, Deborah L ; Bluthner, Martin ; Tan, Eng M</creator><creatorcontrib>Pollard, K. Michael ; Pearson, Deborah L ; Bluthner, Martin ; Tan, Eng M</creatorcontrib><description>The heavy metal mercury elicits a genetically restricted autoantibody response in mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent feature of mercury-induced cell death was the generation of a 19-kDa fragment of fibrillarin that was not found following apoptotic or nonapoptotic cell death induced by stimuli other than mercury. Proteolysis of fibrillarin lacking cysteines, and therefore unable to bind mercury, also produced the 19-kDa fragment, suggesting that a mercury-fibrillarin interaction was not necessary for the unique cleavage pattern of this self-Ag. In contrast to immunization with full-length fibrillarin, the 19-kDa fragment produced anti-fibrillarin Abs with some of the properties of the HgCl2-induced anti-fibrillarin response. We propose that cell death following exposure to an autoimmunity-inducing xenobiotic can lead to the generation of novel protein fragments that may serve as sources of antigenic determinants for self-reactive T lymphocytes.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.165.4.2263</identifier><identifier>PMID: 10925315</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; Apoptosis - drug effects ; Apoptosis - genetics ; Apoptosis - immunology ; Autoantibodies - biosynthesis ; Autoantigens - administration & dosage ; Autoantigens - genetics ; Autoantigens - immunology ; Autoantigens - metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone - administration & dosage ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - immunology ; Chromosomal Proteins, Non-Histone - metabolism ; fibrillarin ; Hydrolysis ; Injections, Subcutaneous ; Macrophages - cytology ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - metabolism ; Mercuric Chloride - pharmacology ; Mice ; Mice, Inbred C57BL ; Molecular Weight ; Mutagenesis, Site-Directed ; Peptide Fragments - administration & dosage ; Peptide Fragments - biosynthesis ; Peptide Fragments - genetics ; Peptide Fragments - immunology ; Xenobiotics - pharmacology</subject><ispartof>The Journal of immunology (1950), 2000-08, Vol.165 (4), p.2263-2270</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-fc3c5b03d39b8a9bdea57f4cbbf3d7069065a155f24604fb09a60e94a4e391363</citedby><cites>FETCH-LOGICAL-c409t-fc3c5b03d39b8a9bdea57f4cbbf3d7069065a155f24604fb09a60e94a4e391363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10925315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pollard, K. Michael</creatorcontrib><creatorcontrib>Pearson, Deborah L</creatorcontrib><creatorcontrib>Bluthner, Martin</creatorcontrib><creatorcontrib>Tan, Eng M</creatorcontrib><title>Proteolytic Cleavage of a Self-Antigen Following Xenobiotic-Induced Cell Death Produces a Fragment with Novel Immunogenic Properties</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The heavy metal mercury elicits a genetically restricted autoantibody response in mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent feature of mercury-induced cell death was the generation of a 19-kDa fragment of fibrillarin that was not found following apoptotic or nonapoptotic cell death induced by stimuli other than mercury. Proteolysis of fibrillarin lacking cysteines, and therefore unable to bind mercury, also produced the 19-kDa fragment, suggesting that a mercury-fibrillarin interaction was not necessary for the unique cleavage pattern of this self-Ag. In contrast to immunization with full-length fibrillarin, the 19-kDa fragment produced anti-fibrillarin Abs with some of the properties of the HgCl2-induced anti-fibrillarin response. We propose that cell death following exposure to an autoimmunity-inducing xenobiotic can lead to the generation of novel protein fragments that may serve as sources of antigenic determinants for self-reactive T lymphocytes.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - immunology</subject><subject>Autoantibodies - biosynthesis</subject><subject>Autoantigens - administration & dosage</subject><subject>Autoantigens - genetics</subject><subject>Autoantigens - immunology</subject><subject>Autoantigens - metabolism</subject><subject>Cell Line</subject><subject>Chromosomal Proteins, Non-Histone - administration & dosage</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - immunology</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>fibrillarin</subject><subject>Hydrolysis</subject><subject>Injections, Subcutaneous</subject><subject>Macrophages - cytology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Mercuric Chloride - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Weight</subject><subject>Mutagenesis, Site-Directed</subject><subject>Peptide Fragments - administration & dosage</subject><subject>Peptide Fragments - biosynthesis</subject><subject>Peptide Fragments - genetics</subject><subject>Peptide Fragments - immunology</subject><subject>Xenobiotics - pharmacology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkM1u1DAURi1ERYfCEyAhr2CV4Tr-CV5WUwZGqmglQGJnOclNxpUTD3bSqPs-OB6mSF1Zss_3-d5DyDsGawFCf7pzwzCPwa-ZkmuxLkvFX5AVkxIKpUC9JCuAsixYpapz8jqlOwBQUIpX5JyBLiVnckUeb2OYMPiHyTV049He2x5p6KilP9B3xeU4uR5Hug3eh8WNPf2NY6hdyHyxG9u5wZZu0Ht6hXba01x3vEs5v422H3Cc6OLyw_dwj57u_o2cC_NvGT1gnBymN-Sssz7h26fzgvzafvm5-VZc33zdbS6vi0aAnoqu4Y2sgbdc15-trlu0supEU9cdbytQGpS0ef-uFApEV4O2ClALK5BrxhW_IB9OvYcY_syYJjO41OTh7YhhToZVUvGKywzyE9jEkFLEzhyiG2x8MAzMUb75L99k-UaYo_ycev9UP9cDts8yJ9sZ-HgC9q7fLy6iSYP1PuPMLMvyrOovt4iSHQ</recordid><startdate>20000815</startdate><enddate>20000815</enddate><creator>Pollard, K. Michael</creator><creator>Pearson, Deborah L</creator><creator>Bluthner, Martin</creator><creator>Tan, Eng M</creator><general>Am Assoc Immnol</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20000815</creationdate><title>Proteolytic Cleavage of a Self-Antigen Following Xenobiotic-Induced Cell Death Produces a Fragment with Novel Immunogenic Properties</title><author>Pollard, K. Michael ; Pearson, Deborah L ; Bluthner, Martin ; Tan, Eng M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-fc3c5b03d39b8a9bdea57f4cbbf3d7069065a155f24604fb09a60e94a4e391363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis - immunology</topic><topic>Autoantibodies - biosynthesis</topic><topic>Autoantigens - administration & dosage</topic><topic>Autoantigens - genetics</topic><topic>Autoantigens - immunology</topic><topic>Autoantigens - metabolism</topic><topic>Cell Line</topic><topic>Chromosomal Proteins, Non-Histone - administration & dosage</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - immunology</topic><topic>Chromosomal Proteins, Non-Histone - metabolism</topic><topic>fibrillarin</topic><topic>Hydrolysis</topic><topic>Injections, Subcutaneous</topic><topic>Macrophages - cytology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Mercuric Chloride - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Weight</topic><topic>Mutagenesis, Site-Directed</topic><topic>Peptide Fragments - administration & dosage</topic><topic>Peptide Fragments - biosynthesis</topic><topic>Peptide Fragments - genetics</topic><topic>Peptide Fragments - immunology</topic><topic>Xenobiotics - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pollard, K. Michael</creatorcontrib><creatorcontrib>Pearson, Deborah L</creatorcontrib><creatorcontrib>Bluthner, Martin</creatorcontrib><creatorcontrib>Tan, Eng M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pollard, K. Michael</au><au>Pearson, Deborah L</au><au>Bluthner, Martin</au><au>Tan, Eng M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteolytic Cleavage of a Self-Antigen Following Xenobiotic-Induced Cell Death Produces a Fragment with Novel Immunogenic Properties</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2000-08-15</date><risdate>2000</risdate><volume>165</volume><issue>4</issue><spage>2263</spage><epage>2270</epage><pages>2263-2270</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The heavy metal mercury elicits a genetically restricted autoantibody response in mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent feature of mercury-induced cell death was the generation of a 19-kDa fragment of fibrillarin that was not found following apoptotic or nonapoptotic cell death induced by stimuli other than mercury. Proteolysis of fibrillarin lacking cysteines, and therefore unable to bind mercury, also produced the 19-kDa fragment, suggesting that a mercury-fibrillarin interaction was not necessary for the unique cleavage pattern of this self-Ag. In contrast to immunization with full-length fibrillarin, the 19-kDa fragment produced anti-fibrillarin Abs with some of the properties of the HgCl2-induced anti-fibrillarin response. We propose that cell death following exposure to an autoimmunity-inducing xenobiotic can lead to the generation of novel protein fragments that may serve as sources of antigenic determinants for self-reactive T lymphocytes.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>10925315</pmid><doi>10.4049/jimmunol.165.4.2263</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-1767 |
ispartof | The Journal of immunology (1950), 2000-08, Vol.165 (4), p.2263-2270 |
issn | 0022-1767 1550-6606 |
language | eng |
recordid | cdi_proquest_miscellaneous_17563735 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Animals Apoptosis - drug effects Apoptosis - genetics Apoptosis - immunology Autoantibodies - biosynthesis Autoantigens - administration & dosage Autoantigens - genetics Autoantigens - immunology Autoantigens - metabolism Cell Line Chromosomal Proteins, Non-Histone - administration & dosage Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - immunology Chromosomal Proteins, Non-Histone - metabolism fibrillarin Hydrolysis Injections, Subcutaneous Macrophages - cytology Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Mercuric Chloride - pharmacology Mice Mice, Inbred C57BL Molecular Weight Mutagenesis, Site-Directed Peptide Fragments - administration & dosage Peptide Fragments - biosynthesis Peptide Fragments - genetics Peptide Fragments - immunology Xenobiotics - pharmacology |
title | Proteolytic Cleavage of a Self-Antigen Following Xenobiotic-Induced Cell Death Produces a Fragment with Novel Immunogenic Properties |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T13%3A52%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Proteolytic%20Cleavage%20of%20a%20Self-Antigen%20Following%20Xenobiotic-Induced%20Cell%20Death%20Produces%20a%20Fragment%20with%20Novel%20Immunogenic%20Properties&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Pollard,%20K.%20Michael&rft.date=2000-08-15&rft.volume=165&rft.issue=4&rft.spage=2263&rft.epage=2270&rft.pages=2263-2270&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.165.4.2263&rft_dat=%3Cproquest_cross%3E17563735%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17563735&rft_id=info:pmid/10925315&rfr_iscdi=true |