Antigen presenting cells (APCs) constitutively express major histocompatibility complex class II (MHC-II) molecules, a crucial component of an organism’s adaptive immune response. Mutations in the master regulator of MHC-II (CIITA) are found in a subset of patients with bare lymphocyte syndrome and result in severe immune response defects. Four promoters control expression of CIITA in a cell type specific manner. Each promoter encodes a unique isoform. It is not known whether the unique isoforms have distinct roles. Isoform 1, expressed by dendritic cells and macrophages induced with IFNγ, encodes a domain with homology to a caspase recruitment domain (CARD). Isoform 1 bears the strongest similarity, of all CIITA isoforms, to the nucleotide-binding domain and leucine-rich repeat containing (NLR) gene family. Members of this family have roles in inflammation and pathogen recognition. A gene-targeted mouse model has been designed to determine whether isoform 1 CIITA has a unique role(s) in immune system function. Experiments suggest that isoform 1 CIITA is not required for proper immune system function. Notably, T-cell development and activation appear to be normal, all APCs examined express class II at levels comparable to wild-type, and lacking isoform 1 does not make an organism more susceptible to particular pathogens. These experiments suggest that isoforms 3 and 4 are sufficient for normal immune system development and function.
- Copyright © 2011 by The American Association of Immunologists, Inc.