Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator gene.
MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-gamma-induced MHCII expression on a wide variety of non-bone marrow-derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4(+) T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-gamma-activated cells of the macrophage lineage. pIV(-/-) mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease.
Waldburger
J M
JM
Department of Genetics and Microbiology, University of Geneva Medical School, 1211 Geneva 4, Switzerland.
Suter
T
T
Fontana
A
A
Acha-Orbea
H
H
Reith
W
W
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma