Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-γ-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4+ T-cell activation

Jeanne M. Soos, Jeffrey I. Krieger, Olaf Stüve, Chelsea L. King, Juan Carlos Patarroyo, Ken Aldape, Karolina Wosik, Anthony J. Slavin, Patricia A. Nelson, Jack P. Antel, Scott S. Zamvil

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Malignant gliomas (MGs), lethal human central nervous system (CNS) neoplasms, contain tumor infiltrating lymphocytes (TIL). Although MHC class II molecules are frequently detected on MG cells, suggesting that they may be capable of antigen (Ag) presentation to CD4+ T cells, deficiencies in CD4+ T-cell activation are associated with these nonimmunogenic tumors. We evaluated regulation of the MHC class II transactivator (CIITA), the key intermediate that controls class II expression, in MG cells and tested whether MG cells could process native Ag. After interferon-γ (IFN-γ) stimulation, MG cells upregulated CIITA and class II molecules. IFN-γ-inducible CIITA expression in MG cells, as well as primary human astrocytes, was directed by two CIITA promoters, pIV, the promoter for IFN-γ-inducible CIITA expression in nonprofessional antigen-presenting cells (APC), and pIII, the promoter that directs constitutive CIITA expression in B cells. Both pIII and pIV directed CIITA transcription in vivo in MGs and ex vivo in IFN-γ-activated primary MG cultures. We also demonstrate for the first time that MG cells can process native Ag for presentation to CD4+ MHC class II-restricted Th1 cells, indicating that MG cells can serve as nonprofessional APC. CIITA may be a key target to modulate MHC class II expression, which could augment immunogenicity, Ag presentation, and CD4+ T-cell activation in MG therapy.

Original languageEnglish (US)
Pages (from-to)391-405
Number of pages15
JournalGLIA
Volume36
Issue number3
DOIs
StatePublished - Dec 1 2001

Keywords

  • Antigen-processing
  • Astrocytoma
  • CIITA
  • Gene regulation
  • MHC class II

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-γ-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4<sup>+</sup> T-cell activation'. Together they form a unique fingerprint.

Cite this