Effects of C2ta genetic polymorphisms on MHC class II expression and autoimmune diseases

Abstract

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-2 ) 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-isomerase -peptide-induced arthritis), or multiple sclerosis (MOG protein-induced and MOG 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.

The Major Histocompatibility Complex Class III Haplotype Ltab-Ncr3 Regulates Adjuvant-Induced but Not Antigen-Induced Autoimmunity

“…and J.T.). As previously described, 25 EAE was monitored on a scoring scale as follows: 0 Z normal; 1 Z tail weakness; 2 Z tail paralysis; 3 Z mild waddling movement; 4 Z heavy waddling movement, unsecure foothold; 5 Z paralysis of a limb, crawling; 6 Z paralysis of a pair of limbs; 7 Z paralysis of all four limbs; and 8 Z death. Animals were euthanized when they reached score 7. ajp.amjpathol.org -The American Journal of Pathology All experiments were approved by the Stockholm Ethical Committee and performed in accordance with the guidelines of the Swedish National Board for Laboratory Animals and the European Community Council Directive (86/609/EEC).…”

Tim-3 Relieves Experimental Autoimmune Encephalomyelitis by Suppressing MHC-II

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