Cutting edge

Induction of the antigen-processing enzyme IFN-γ-inducible lysosomal thiol reductase in melanoma cells is STAT1-dependent but CIITA-independent

Patrick W. O'Donnell, Azizul Haque, Michael Klemsz, Mark Kaplan, Janice Blum

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Presentation and CD4+ T cell responses to Ag in the context of MHC class II molecules require processing of native proteins into short peptide fragments. Within this pathway, IFN-γ-inducible lysosomal thiol reductase (GILT) functions to catalyze thiol bond reduction, thus unfolding native protein Ag and facilitating further processing via cellular proteases. In contrast with professional APCs such as B cells, class II-positive human melanomas expressed relatively little to no GIL protein or mRNA. Tumor cell GILT expression was partially restored with IFN-γ treatment but unlike other genes required for class II Ag presentation, GILT was not regulated by CIITA. Rather, studies revealed STAT1 plays a direct role in IFN-γ-inducible GILT expression. These results define a molecular mechanism for the uncoupled regulation of MHC class II genes and the processing enzyme GILT in human melanomas.

Original languageEnglish (US)
Pages (from-to)731-735
Number of pages5
JournalJournal of Immunology
Volume173
Issue number2
StatePublished - Jul 15 2004
Externally publishedYes

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MHC Class II Genes
Antigen Presentation
Sulfhydryl Compounds
Melanoma
Oxidoreductases
Protein Unfolding
Peptide Fragments
Enzymes
Proteins
Peptide Hydrolases
B-Lymphocytes
T-Lymphocytes
Messenger RNA
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

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abstract = "Presentation and CD4+ T cell responses to Ag in the context of MHC class II molecules require processing of native proteins into short peptide fragments. Within this pathway, IFN-γ-inducible lysosomal thiol reductase (GILT) functions to catalyze thiol bond reduction, thus unfolding native protein Ag and facilitating further processing via cellular proteases. In contrast with professional APCs such as B cells, class II-positive human melanomas expressed relatively little to no GIL protein or mRNA. Tumor cell GILT expression was partially restored with IFN-γ treatment but unlike other genes required for class II Ag presentation, GILT was not regulated by CIITA. Rather, studies revealed STAT1 plays a direct role in IFN-γ-inducible GILT expression. These results define a molecular mechanism for the uncoupled regulation of MHC class II genes and the processing enzyme GILT in human melanomas.",
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AU - Blum, Janice

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