Major histocompatibility complex‐controlled protective influences on experimental autoimmune encephalomyelitis are peptide specific

Abstract

Abstract The myelin basic protein (MBP) peptide 63–88‐induced experimental autoimmune encephalomyelitis (EAE) and its associated T cell cytokine profile are influenced by the rat major histocompatibility complex (MHC). There is an allele‐specific protective influence of the MHC class I region, whereas the MHC class II region display either disease‐protective or ‐promoting effects. To investigate if the MHC‐associated protection is dependent on certain combinations of MBP peptide and MHC molecules, we have now used another peptide (MBP 89–101). A broader and different set of rat MHC alleles were associated with EAE induced with MBP 89–101 as compared to MBP 63–88. All EAE‐susceptible strains mounted peptide‐specific strong T helper (Th) 1‐like immune responses in vitro. Immunization of rats with an extended peptide (MBP 87–110) induced EAE associated with the same MHC haplotypes as the 89–101 peptide, except in LEW.1N (RT1 n ) rats which were relatively resistant. Only this strain responded with additional Th2‐like and transforming growth factor‐β responses to the peptide in vitro. In vivo depletion of CD8 + cells aggravated the disease in this strain. We conclude that both MHC‐controlled promoting and protective influences on EAE are dependent on certain MHC/MBP peptide combinations, and that the 87–110 region of MBP contains a major MHC‐associated encephalitogenic epitope in the rat.