| First Author | Yau AC | Year | 2017 |
| Journal | Immunology | Volume | 150 |
| Issue | 4 | Pages | 408-417 |
| PubMed ID | 27861821 | Mgi Jnum | J:246187 |
| Mgi Id | MGI:5923582 | Doi | 10.1111/imm.12692 |
| Citation | Yau AC, et al. (2017) Effects of C2ta genetic polymorphisms on MHC class II expression and autoimmune diseases. Immunology 150(4):408-417 |
| abstractText | Antigen presentation by the MHC-II to CD4+ T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variations in CIITA have been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2q ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function. We demonstrate that an allelic variant in the type I promoter of C2ta resulted in an increased expression of MHC-II on macrophages (72-151% higher mean florescence intensity) and conventional dendritic cells (13-65% higher mean florescence intensity) in both spleen and peripheral blood. The increase in MHC-II expression resulted in an increase in antigen presentation to T cells in vitro and increased T-cell activation. The differential MHC-II expression in B6Q.C2ta, however, did not alter the disease development in models of rheumatoid arthritis (collagen-induced arthritis and human glucose-6-phosphate-isomerase325-339 -peptide-induced arthritis), or multiple sclerosis (MOG1-125 protein-induced and MOG79-96 peptide-induced experimental autoimmune encephalomyelitis). This is the first study to address the role of an allelic variant in type I promoter of C2ta in MHC-II expression and autoimmune diseases; and shows that C2ta polymorphisms regulate MHC-II expression and T-cell responses but do not necessarily have a strong impact on autoimmune diseases. |
