Regulation of class II MHC expression in APCs: roles of types I, III, and IV class II transactivator.
Class II transactivator (CIITA) is necessary for expression of class II MHC (MHC-II) molecules. In mice, CIITA expression is regulated by three promoters (pI, pIII, and pIV), producing types I, III, and IV CIITA. The relative roles of different CIITA types remain unclear. Unstimulated bone marrow-derived macrophages expressed low levels of CIITA mRNA; type I CIITA was nine times more abundant than type IV (type III CIITA was barely detected). Exposure to IFN-gamma (6 h) dramatically increased types I and IV CIITA mRNA to similar absolute levels. Type IV CIITA declined over time, but type I was stable for over 72 h. Thus, the dominant form of CIITA evolved with time during activation by IFN-gamma, and type I CIITA explained prolonged expression of MHC-II by macrophages. mRNA half-life was shorter for type I than type IV CIITA, suggesting that sustained transcription contributed to stable expression of type I CIITA induced by IFN-gamma. Splenic B cells expressed mRNA for type III CIITA but very little for types I or IV. Treatment with IL-4 increased surface expression of MHC-II protein, but mRNA for MHC-II and CIITA (total, I, III, and IV) remained unchanged, suggesting posttranslational regulation. Splenic dendritic cells expressed type I CIITA but little type III or IV; CpG DNA induced their maturation and decreased types I and III CIITA, consistent with decreased MHC-II protein synthesis. CIITA types differ in regulation in various APCs under different stimuli, and the predominant type of CIITA varies at different stages of APC activation.
Department of Pathology and Division of Infectious Disease, Case Western Reserve University, Cleveland, OH 44106, USA.
Rish K
RK
Pai
David
D
Askew
W Henry
WH
Boom
Clifford V
CV
Harding
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009687:Nuclear Proteins; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000145:classification / Q000235:genetics / Q000502:physiology*
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D015847:Interleukin-4; D007371:Interferon-gamma