Mice lacking the MHC class II transactivator (CIITA) show tissue-specific impairment of MHC class II expression.
CIITA activates the expression of multiple genes involved in antigen presentation and it is believed to be required for both constitutive and IFN gamma-inducible expression of these genes. To understand the role of CIITA in vivo, we have used gene targeting to generate mice that lack CIITA. CIITA-deficient (-/-) mice do not express conventional MHC class II molecules on the surface of splenic B cells and dendritic cells. In addition, macrophages resident in the peritoneal cavity do not express MHC class II molecules upon IFN gamma stimulation nor do somatic tissues of mice injected with IFN gamma, in contrast with wild-type mice. The levels of Ii and H-2M gene transcripts are substantially decreased but absent in CIITA (-/-) mice. The transcription of nonconventional MHC class II genes is, however not affected by CIITA deficiency. A subset of thymic epithelial cells express MHC class II molecules. Nonetheless, very few mature CD4 T cells are present in the periphery of CIITA (-/-) mice despite MHC class II expression in the thymus. Consequently, CIITA(-/-) mice are impaired in T-dependent antigen responses and MHC class II-mediated allogeneic responses.
Chang
C H
CH
Howard Hughes Medical Institute, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Guerder
S
S
Hong
S C
SC
van Ewijk
W
W
Flavell
R A
RA
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000276:immunology
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma