THE MAJOR HISTOCOMPATIBILITY COMPLEX INFLUENCES MYELIN BASIC-PROTEIN 63-88-INDUCED T-CELL CYTOKINE PROFILE AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Polymorphism of the major histocompatibility complex (MHC) influences susceptibility to experimental autoimmune encephalomyelitis (EAE) indu ced by myelin basic protein (MBP) in rats. Current concepts relate suc h influences to the capacity of class II molecules to present relevant peptides to autoreactive T cells. We have here analyzed the MHC influ ence on the immune response and the development of EAE after immunizat ion with the immunodominant peptide MBP-63-88. Analysis of MHC-congeni c LEWIS strains showed that RT1a, RT1c and RT1l haplotypes are permiss ive for disease induction, whereas RT1d and RT1u are resistant. All EA E responding strains showed peptide-specific proliferation and interfe ron (IFN)-gamma secretion, but no early significant tendency to expres s interleukin (IL-4) or transforming growth factor (TGF)-beta mRNA in lymphocytes in response to the MBP 63-88, 7 days post immunization (p. i.). Later, 14 days p.i., peptide-specific induction of IL-4 and TGF-b eta occurred in RT1l rats. Among the EAE non-responders strains, only the RT1u rats showed an immune response to MBP 63-88. This response, h owever, was qualitatively different from the immune response in the EA E-susceptible strains. Thus, there was no proliferation and only moder ate IFN-gamma production in response to peptide, but in contrast, a si gnificant and early peptide-induced IL-4 and TGF-beta response was obs erved. The data suggest that the MHC-associated susceptibility to EAE is partly related to the ability to mount a TH1-like immune response w hile the MHC-associated EAE resistance may either be related to MBP pe ptide non-responsiveness or to peptide recognition and induction of a qualitatively different and disease down-regulatory immune response.