Affiliation: | a Department of Immunobiology (B.A.’tH., H.P.M.B., S.A., R.E.B.), Biomedical Primate Research Centre, Rijswijk, The Netherlands b Department of Immunology (B.A.’tH.), Erasmus University, Rotterdam, The Netherlands c Department of Pharmacology and Pathophysiology (B.A.’tH.), University of Utrecht, Utrecht, The Netherlands d Department of Immunohaematology and Bloodbank (R.E.B.), Leiden University Medical Center, Leiden, The Netherlands |
Abstract: | Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease primarily affecting the central nervous system. Of the many candidate polymorphic major histocompatibility complex (MHC) and non-MHC genes contributing to disease susceptibility, including those encoding effector (cytokines and chemokines) or receptor molecules within the immune system (MHC, TCR, Ig or FcR), human leukocyte antigen (HLA) class II genes have the most significant influence. In this article we put forward the hypothesis that the influence of HLA genes on the risk to develop MS is actually the sum of multiple antigen presenting cell (APC) and T-cell interactions involving HLA class I and class II molecules. This article will also discuss that, because of the genetic and immunologic similarity to humans, autoimmune models of MS in non-human primates are the experimental models “par excellence” to test this hypothesis. |