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
Hauptverfasser: Turnquist, Heth R, Kohlgraf, Karl G, McIlhaney, Mary M, Mosley, R Lee, Hollingsworth, Michael A, Solheim, Joyce C
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container_end_page 470
container_issue 4
container_start_page 462
container_title Journal of clinical immunology
container_volume 24
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.
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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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