Efficient and Qualitatively Distinct MHC Class I-Restricted Presentation of Antigen Targeted to the Endoplasmic Reticulum
For most nascent glycoprotein Ags, the MHC class I-restricted processing pathway begins in the endoplasmic reticulum (ER). From this location, they are translocated to the cytosol for degradation by the proteasome. A reasonable assumption is that processing of exocytic Ags is less efficient than tha...
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| Veröffentlicht in: | The Journal of immunology (1950) 2002-03, Vol.168 (6), p.2667-2675 |
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| container_title | The Journal of immunology (1950) |
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| creator | Golovina, Tatiana N Wherry, E. John Bullock, Timothy N. J Eisenlohr, Laurence C |
| description | For most nascent glycoprotein Ags, the MHC class I-restricted processing pathway begins in the endoplasmic reticulum (ER). From this location, they are translocated to the cytosol for degradation by the proteasome. A reasonable assumption is that processing of exocytic Ags is less efficient than that of cytosolic Ags, due to the requirement for additional handling, but that the processing pathways for the two types of proteins are otherwise similar. To test this, we compared the presentation of three epitopes within influenza nucleoprotein (NP) when this Ag is targeted to the cytosol or the ER. Surprisingly, under conditions of limited Ag expression, presentation of two proteasome-dependent epitopes is comparable when NP is targeted to the ER while presentation of a third is negatively impacted. Furthermore, presentation of the third epitope is unaffected by the addition of proteasome inhibitor when cytosolic NP is expressed but is significantly enhanced when exocytic NP is expressed. These results indicate that delivery of Ag to the ER need not preclude efficient presentation and that processing of cytosolic and ER-targeted Ag is qualitatively distinct. |
| doi_str_mv | 10.4049/jimmunol.168.6.2667 |
| format | Article |
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Furthermore, presentation of the third epitope is unaffected by the addition of proteasome inhibitor when cytosolic NP is expressed but is significantly enhanced when exocytic NP is expressed. These results indicate that delivery of Ag to the ER need not preclude efficient presentation and that processing of cytosolic and ER-targeted Ag is qualitatively distinct.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.168.6.2667</identifier><identifier>PMID: 11884431</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>3T3 Cells ; Acetylcysteine - analogs & derivatives ; Acetylcysteine - pharmacology ; Animals ; Antigen Presentation - drug effects ; Antigen Presentation - genetics ; Cysteine Endopeptidases ; Cysteine Proteinase Inhibitors - pharmacology ; Cytosol - enzymology ; Cytosol - immunology ; Cytosol - metabolism ; Endoplasmic Reticulum - enzymology ; Endoplasmic Reticulum - genetics ; Endoplasmic Reticulum - immunology ; Endoplasmic Reticulum - metabolism ; Epitopes - biosynthesis ; Epitopes - immunology ; Epitopes - metabolism ; Female ; Gene Targeting ; H-2 Antigens - immunology ; Influenza A virus - genetics ; Influenza A virus - immunology ; L Cells (Cell Line) ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Multienzyme Complexes - antagonists & inhibitors ; Nucleoproteins - genetics ; Nucleoproteins - immunology ; Nucleoproteins - metabolism ; Peptide Fragments - biosynthesis ; Peptide Fragments - immunology ; Peptide Fragments - metabolism ; Proteasome Endopeptidase Complex ; proteasomes ; Protein Transport - genetics ; Protein Transport - immunology ; RNA-Binding Proteins ; Viral Core Proteins - genetics ; Viral Core Proteins - immunology ; Viral Core Proteins - metabolism</subject><ispartof>The Journal of immunology (1950), 2002-03, Vol.168 (6), p.2667-2675</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-e46c0969bca68f92be5719a8829943197e30080c8847161219903ffca0be6d003</citedby><cites>FETCH-LOGICAL-c475t-e46c0969bca68f92be5719a8829943197e30080c8847161219903ffca0be6d003</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/11884431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Golovina, Tatiana N</creatorcontrib><creatorcontrib>Wherry, E. John</creatorcontrib><creatorcontrib>Bullock, Timothy N. J</creatorcontrib><creatorcontrib>Eisenlohr, Laurence C</creatorcontrib><title>Efficient and Qualitatively Distinct MHC Class I-Restricted Presentation of Antigen Targeted to the Endoplasmic Reticulum</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>For most nascent glycoprotein Ags, the MHC class I-restricted processing pathway begins in the endoplasmic reticulum (ER). From this location, they are translocated to the cytosol for degradation by the proteasome. A reasonable assumption is that processing of exocytic Ags is less efficient than that of cytosolic Ags, due to the requirement for additional handling, but that the processing pathways for the two types of proteins are otherwise similar. To test this, we compared the presentation of three epitopes within influenza nucleoprotein (NP) when this Ag is targeted to the cytosol or the ER. Surprisingly, under conditions of limited Ag expression, presentation of two proteasome-dependent epitopes is comparable when NP is targeted to the ER while presentation of a third is negatively impacted. Furthermore, presentation of the third epitope is unaffected by the addition of proteasome inhibitor when cytosolic NP is expressed but is significantly enhanced when exocytic NP is expressed. These results indicate that delivery of Ag to the ER need not preclude efficient presentation and that processing of cytosolic and ER-targeted Ag is qualitatively distinct.</description><subject>3T3 Cells</subject><subject>Acetylcysteine - analogs & derivatives</subject><subject>Acetylcysteine - pharmacology</subject><subject>Animals</subject><subject>Antigen Presentation - drug effects</subject><subject>Antigen Presentation - genetics</subject><subject>Cysteine Endopeptidases</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Cytosol - enzymology</subject><subject>Cytosol - immunology</subject><subject>Cytosol - metabolism</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Endoplasmic Reticulum - genetics</subject><subject>Endoplasmic Reticulum - immunology</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Epitopes - biosynthesis</subject><subject>Epitopes - immunology</subject><subject>Epitopes - metabolism</subject><subject>Female</subject><subject>Gene Targeting</subject><subject>H-2 Antigens - immunology</subject><subject>Influenza A virus - genetics</subject><subject>Influenza A virus - immunology</subject><subject>L Cells (Cell Line)</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Multienzyme Complexes - antagonists & inhibitors</subject><subject>Nucleoproteins - genetics</subject><subject>Nucleoproteins - immunology</subject><subject>Nucleoproteins - metabolism</subject><subject>Peptide Fragments - biosynthesis</subject><subject>Peptide Fragments - immunology</subject><subject>Peptide Fragments - metabolism</subject><subject>Proteasome Endopeptidase Complex</subject><subject>proteasomes</subject><subject>Protein Transport - genetics</subject><subject>Protein Transport - immunology</subject><subject>RNA-Binding Proteins</subject><subject>Viral Core Proteins - genetics</subject><subject>Viral Core Proteins - immunology</subject><subject>Viral Core Proteins - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EomnpL0BCPsFpw3g__HGs0tBWKmqp2rPleGcTV15vWHuJ8u9xlCC4cZrL874zo4eQjwzmNdTq66vr-ykMfs64nPN5ybl4Q2asaaDgHPhbMgMoy4IJLs7IeYyvAMChrN-TM8akrOuKzch-2XXOOgyJmtDSH5PxLpnkfqHf02sXkws20e-3C7rwJkZ6VzxhTKOzCVv6OGLMyYwPgQ4dvQrJrTHQZzOu8QCkgaYN0mVoh22O987SJ0zOTn7qP5B3nfERL0_zgrx8Wz4vbov7h5u7xdV9YWvRpAJrbkFxtbKGy06VK2wEU0bKUqn8gRJYAUiw-SHBOCuZUlB1nTWwQt4CVBfk87F3Ow4_p3y87l206L0JOExRC9YAk6L5L8jyyqqsZQarI2jHIcYRO70dXW_GvWagD2r0HzU6q9FcH9Tk1KdT_bTqsf2bObnIwJcjsHHrzc6NqGNvvM8407vd7p-q37JvmmA</recordid><startdate>20020315</startdate><enddate>20020315</enddate><creator>Golovina, Tatiana N</creator><creator>Wherry, E. 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J ; Eisenlohr, Laurence C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-e46c0969bca68f92be5719a8829943197e30080c8847161219903ffca0be6d003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>3T3 Cells</topic><topic>Acetylcysteine - analogs & derivatives</topic><topic>Acetylcysteine - pharmacology</topic><topic>Animals</topic><topic>Antigen Presentation - drug effects</topic><topic>Antigen Presentation - genetics</topic><topic>Cysteine Endopeptidases</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Cytosol - enzymology</topic><topic>Cytosol - immunology</topic><topic>Cytosol - metabolism</topic><topic>Endoplasmic Reticulum - enzymology</topic><topic>Endoplasmic Reticulum - genetics</topic><topic>Endoplasmic Reticulum - immunology</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Epitopes - biosynthesis</topic><topic>Epitopes - immunology</topic><topic>Epitopes - metabolism</topic><topic>Female</topic><topic>Gene Targeting</topic><topic>H-2 Antigens - immunology</topic><topic>Influenza A virus - genetics</topic><topic>Influenza A virus - immunology</topic><topic>L Cells (Cell Line)</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Multienzyme Complexes - antagonists & inhibitors</topic><topic>Nucleoproteins - genetics</topic><topic>Nucleoproteins - immunology</topic><topic>Nucleoproteins - metabolism</topic><topic>Peptide Fragments - biosynthesis</topic><topic>Peptide Fragments - immunology</topic><topic>Peptide Fragments - metabolism</topic><topic>Proteasome Endopeptidase Complex</topic><topic>proteasomes</topic><topic>Protein Transport - genetics</topic><topic>Protein Transport - immunology</topic><topic>RNA-Binding Proteins</topic><topic>Viral Core Proteins - genetics</topic><topic>Viral Core Proteins - immunology</topic><topic>Viral Core Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Golovina, Tatiana N</creatorcontrib><creatorcontrib>Wherry, E. John</creatorcontrib><creatorcontrib>Bullock, Timothy N. J</creatorcontrib><creatorcontrib>Eisenlohr, Laurence C</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><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Golovina, Tatiana N</au><au>Wherry, E. John</au><au>Bullock, Timothy N. 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To test this, we compared the presentation of three epitopes within influenza nucleoprotein (NP) when this Ag is targeted to the cytosol or the ER. Surprisingly, under conditions of limited Ag expression, presentation of two proteasome-dependent epitopes is comparable when NP is targeted to the ER while presentation of a third is negatively impacted. Furthermore, presentation of the third epitope is unaffected by the addition of proteasome inhibitor when cytosolic NP is expressed but is significantly enhanced when exocytic NP is expressed. These results indicate that delivery of Ag to the ER need not preclude efficient presentation and that processing of cytosolic and ER-targeted Ag is qualitatively distinct.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11884431</pmid><doi>10.4049/jimmunol.168.6.2667</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 3T3 Cells Acetylcysteine - analogs & derivatives Acetylcysteine - pharmacology Animals Antigen Presentation - drug effects Antigen Presentation - genetics Cysteine Endopeptidases Cysteine Proteinase Inhibitors - pharmacology Cytosol - enzymology Cytosol - immunology Cytosol - metabolism Endoplasmic Reticulum - enzymology Endoplasmic Reticulum - genetics Endoplasmic Reticulum - immunology Endoplasmic Reticulum - metabolism Epitopes - biosynthesis Epitopes - immunology Epitopes - metabolism Female Gene Targeting H-2 Antigens - immunology Influenza A virus - genetics Influenza A virus - immunology L Cells (Cell Line) Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Multienzyme Complexes - antagonists & inhibitors Nucleoproteins - genetics Nucleoproteins - immunology Nucleoproteins - metabolism Peptide Fragments - biosynthesis Peptide Fragments - immunology Peptide Fragments - metabolism Proteasome Endopeptidase Complex proteasomes Protein Transport - genetics Protein Transport - immunology RNA-Binding Proteins Viral Core Proteins - genetics Viral Core Proteins - immunology Viral Core Proteins - metabolism |
| title | Efficient and Qualitatively Distinct MHC Class I-Restricted Presentation of Antigen Targeted to the Endoplasmic Reticulum |
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