CIITA promoter I CARD-deficient mice express functional MHC class II genes in myeloid and lymphoid compartments

Abstract

Three distinct promoters control the master regulator of MHC class II expression, CIITA, in a cell type specific manner. Promoter I (pI) CIITA, expressed primarily by dendritic cells and macrophages, expresses a unique isoform that contains a caspase recruitment domain. The activity and function of this isoform is not understood but has been thought to enhance the function of CIITA in antigen presenting cells. To determine if isoform I of CIITA has specific functions, CIITA mutant mice were created in which isoform I was replaced with isoform III sequences. Mice in which pI and the CARD encoding exon were deleted were also created. No defect in the formation of CD4 T cells, the ability to respond to a model antigen, or bacterial or viral challenge was observed in mice lacking CIITA isoform I. Although CIITA and MHC-II expression was decreased in splenic DC, the pI knockout animals expressed CIITA from downstream promoters, suggesting that control of pI activity is mediated by unknown s II distal elements that could act at the pIII, the B cell promoter. Thus, no critical function is linked to the CARD domain of CIITA isoform I with respect to basic immune system development, function and challenge.