Tapasin decreases immune responsiveness to a model tumor antigen
The T-cell response against cancer is dependent on the cell surface presentation of tumor-associated or tumor-specific peptides by major histocompatibility complex (MHC) class I molecules. We found that tapasin, a chaperone protein that normally assists in the assembly of MHC class I molecules, is u...
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Veröffentlicht in: | Journal of clinical immunology 2004-07, Vol.24 (4), p.462-470 |
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creator | Turnquist, Heth R Kohlgraf, Karl G McIlhaney, Mary M Mosley, R Lee Hollingsworth, Michael A Solheim, Joyce C |
description | The T-cell response against cancer is dependent on the cell surface presentation of tumor-associated or tumor-specific peptides by major histocompatibility complex (MHC) class I molecules. We found that tapasin, a chaperone protein that normally assists in the assembly of MHC class I molecules, is undetectable in an unstimulated pancreatic tumor cell line, Panc02, and only very weakly expressed after gamma-interferon stimulation. Transfection of tapasin into the Panc02 cells did not quantitatively increase MHC class I surface expression or detectably affect MHC class I association with peptide and beta(2)-microglubulin (beta(2)m). However, we found that transfected tapasin downregulated immune reactivity against a model tumor antigen, MUC1. Although tapasin has been previously shown by others to increase immune recognition of particular antigens, our results suggest that tapasin has a negative impact on the presentation of an immunodominant epitope from a specific model tumor antigen. |
doi_str_mv | 10.1023/B:JOCI.0000029118.51587.d9 |
format | Article |
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We found that tapasin, a chaperone protein that normally assists in the assembly of MHC class I molecules, is undetectable in an unstimulated pancreatic tumor cell line, Panc02, and only very weakly expressed after gamma-interferon stimulation. Transfection of tapasin into the Panc02 cells did not quantitatively increase MHC class I surface expression or detectably affect MHC class I association with peptide and beta(2)-microglubulin (beta(2)m). However, we found that transfected tapasin downregulated immune reactivity against a model tumor antigen, MUC1. Although tapasin has been previously shown by others to increase immune recognition of particular antigens, our results suggest that tapasin has a negative impact on the presentation of an immunodominant epitope from a specific model tumor antigen.</description><identifier>ISSN: 0271-9142</identifier><identifier>EISSN: 1573-2592</identifier><identifier>DOI: 10.1023/B:JOCI.0000029118.51587.d9</identifier><identifier>PMID: 15163903</identifier><identifier>CODEN: JCIMDO</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Antibody Formation - drug effects ; Antigens - immunology ; Antigens, Neoplasm - immunology ; Antiporters - genetics ; Antiporters - pharmacology ; Cell Line, Tumor ; Down-Regulation - drug effects ; Glycoproteins - immunology ; Histocompatibility Antigens Class I - genetics ; Humans ; Immunodominant Epitopes ; Immunoglobulins - genetics ; Immunoglobulins - pharmacology ; Membrane Transport Proteins ; Molecular Chaperones - genetics ; Molecular Chaperones - pharmacology ; Mucin-1 ; Mucins ; Pancreatic Neoplasms - pathology ; Transfection</subject><ispartof>Journal of clinical immunology, 2004-07, Vol.24 (4), p.462-470</ispartof><rights>Copyright Kluwer Academic Publishers Jul 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-2cc514b11b546d09a94a3d1390a8391dcc3d28832ac182b2fa09c93d59420be73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15163903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Turnquist, Heth R</creatorcontrib><creatorcontrib>Kohlgraf, Karl G</creatorcontrib><creatorcontrib>McIlhaney, Mary M</creatorcontrib><creatorcontrib>Mosley, R Lee</creatorcontrib><creatorcontrib>Hollingsworth, Michael A</creatorcontrib><creatorcontrib>Solheim, Joyce C</creatorcontrib><title>Tapasin decreases immune responsiveness to a model tumor antigen</title><title>Journal of clinical immunology</title><addtitle>J Clin Immunol</addtitle><description>The T-cell response against cancer is dependent on the cell surface presentation of tumor-associated or tumor-specific peptides by major histocompatibility complex (MHC) class I molecules. We found that tapasin, a chaperone protein that normally assists in the assembly of MHC class I molecules, is undetectable in an unstimulated pancreatic tumor cell line, Panc02, and only very weakly expressed after gamma-interferon stimulation. Transfection of tapasin into the Panc02 cells did not quantitatively increase MHC class I surface expression or detectably affect MHC class I association with peptide and beta(2)-microglubulin (beta(2)m). However, we found that transfected tapasin downregulated immune reactivity against a model tumor antigen, MUC1. 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subjects | Antibody Formation - drug effects Antigens - immunology Antigens, Neoplasm - immunology Antiporters - genetics Antiporters - pharmacology Cell Line, Tumor Down-Regulation - drug effects Glycoproteins - immunology Histocompatibility Antigens Class I - genetics Humans Immunodominant Epitopes Immunoglobulins - genetics Immunoglobulins - pharmacology Membrane Transport Proteins Molecular Chaperones - genetics Molecular Chaperones - pharmacology Mucin-1 Mucins Pancreatic Neoplasms - pathology Transfection |
title | Tapasin decreases immune responsiveness to a model tumor antigen |
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