HLA-DP - A CLASS-II RESTRICTION MOLECULE INVOLVED IN EPITOPE SPREADING DURING THE DEVELOPMENT OF MULTIPLE-SCLEROSIS

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic i nheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease ris k vs disease outcome may be associated with distinctly different HLA c lass II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognitio n with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II allel es, we did observe epitope spreading to the p50-63 determinant of myel in proteolipid protein (PLP) in two study subjects showing complete di sparity at HLA-DR and -DQ bur identity at the HLA-DP allele DPB10301. In the present study we show that self-recognition during the early s tages In the development of MS involves HLA-DP class II restrict ed re sponses to the PLP 50-63 spreading determinant. Our results suggest-ha t self-presentation by HLA-DP may play an important role in epitope sp reading and in the propagating of self-recognition during che clinical progression of MS. (C) American Society for Histocompatibility and Im munogenetics, 1998. Published by Elsevier Science Inc.