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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Sprache:eng
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Zusammenfassung: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.
ISSN:0271-9142
1573-2592
DOI:10.1023/B:JOCI.0000029118.51587.d9