Multiple Sclerosis (MS) is an AutoImmune DeMyelinating Disease of the Central Nervous System.

It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ Class II Genes contribute to MS susceptibility.

And, current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA Class II alleles.

We have recently shown the early development of MS is accompanied by an extensive plasticity of Myelin Self-Recognition with the acquisition of NeoAutoReactivity, 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 alleles, we did observe Epitope spreading to the p50-63 determinant of Myelin ProteoLipid Protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1*0301.

In the present study we show that Self-Recognition during the early stages in the development of MS involves HLA-DP Class II restricted responses to the PLP 50-63 spreading determinant.