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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
Author(s) -
Soos Jeanne M.,
Krieger Jeffrey I.,
Stüve Olaf,
King Chelsea L.,
Patarroyo Juan Carlos,
Aldape Ken,
Wosik Karolina,
Slavin Anthony J.,
Nelson Patricia A.,
Antel Jack P.,
Zamvil Scott S.
Publication year - 2001
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.1125
Subject(s) - ciita , mhc class ii , biology , antigen presentation , antigen presenting cell , cancer research , antigen processing , microbiology and biotechnology , antigen , mhc class i , t cell , major histocompatibility complex , immune system , immunology
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. GLIA 36:391–405, 2001. © 2001 Wiley‐Liss, Inc.