Disparate MHC class II haplotypes in myelin oligodendrocyte glycoprotein- and myelin basic protein-induced...

The major histocompatibility complex (MHC) regulates multiple sclerosis (MS) and its model experimental autoimmune encephalomyelitis (EAE). We created four new intra-MHC recombinant rat strains, between the MHC haplotypes RT1(n) (BN) and RT1(l) (LEW) on the LEW background, to define disease regulation and localization within the MHC. Immunization with recombinant myelin oligodendrocyte glycoprotein (a.a.1-125; MOG)/IFA induced EAE in strains expressing the MHC class II allele RT1.B(n), whereas strains expressing the RT1.B(l) were resistant. In myelin basic protein peptide (MBP(GP)63-88)/CFA-induced EAE, RT1.B(l) expressing strains were susceptible whereas strains expressing the RT1.B(n) were resistant. High levels of antigen-specific IFN-gamma secreting lymphoid cells and antigen-specific serum IgG antibodies were only recorded in rats with an MHC class II allele that permitted MOG- or MBP-EAE, respectively. Genetically, we localized the MHC regulation of the investigated EAE models to the central part of the MHC, containing the MHC class II (RT1.B/D) and the centromeric parts of the MHC class III. No influences were evident from the classical MHC class I (RT1.A), the telomeric parts of the MHC class III or the non-classical MHC class I (RT1.C/E/M) in contrast to previous reports. The MHC class II haplotype-specific regulation of EAE induced with two different CNS antigens demonstrates a strikingly specific MHC-association even within the same target organ.