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 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.
Turnquist
Heth R
HR
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Kohlgraf
Karl G
KG
McIlhaney
Mary M
MM
Mosley
R Lee
RL
Hollingsworth
Michael A
MA
Solheim
Joyce C
JC
D000917:Antibody Formation / Q000187:drug effects*; D000941:Antigens / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D017920:Antiporters / Q000235:genetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes; D007136:Immunoglobulins / Q000235:genetics / Q000494:pharmacology*; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones / Q000235:genetics / Q000494:pharmacology; D018396:Mucin-1; D009077:Mucins; D010190:Pancreatic Neoplasms / Q000473:pathology; D014162:Transfection
D000941:Antigens; D000951:Antigens, Neoplasm; D017920:Antiporters; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D007136:Immunoglobulins; C060192:MUC1 protein, human; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D018396:Mucin-1; D009077:Mucins; C107762:tapasin