Literature DB >> 15163903

Tapasin decreases immune responsiveness to a model tumor antigen.

Heth R Turnquist1, Karl G Kohlgraf, Mary M McIlhaney, R Lee Mosley, Michael A Hollingsworth, Joyce C Solheim.   

Abstract

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.

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Year:  2004        PMID: 15163903     DOI: 10.1023/B:JOCI.0000029118.51587.d9

Source DB:  PubMed          Journal:  J Clin Immunol        ISSN: 0271-9142            Impact factor:   8.317


  31 in total

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2.  Functional deficiencies of components of the MHC class I antigen pathway in human tumors of epithelial origin.

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4.  A sequential model for peptide binding and transport by the transporters associated with antigen processing.

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5.  Localization of allodeterminants on H-2Kb antigens determined with monoclonal antibodies and H-2 mutant mice.

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6.  Quantitative and qualitative influences of tapasin on the class I peptide repertoire.

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7.  Increased tumorigenicity, but unchanged immunogenicity, of transporter for antigen presentation 1-deficient tumors.

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9.  Interaction of MHC class I molecules with the transporter associated with antigen processing.

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10.  Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice.

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Review 3.  Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation.

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