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.
Pai
Rish K
RK
Department of Pathology and Division of Infectious Disease, Case Western Reserve University, Cleveland, OH 44106, USA.
Askew
David
D
Boom
W Henry
WH
Harding
Clifford V
CV
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