J Immunol 2001 Dec 15;167(12):7119-7125
Forsthuber TG, Shive CL, Wienhold W, de Graaf K, Spack EG, Sublett R, Melms A, Kort J, Racke MK, Weissert R.
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106. Department of Neurology, University of Tubingen, Tubingen, Germany. InterMune, Brisbane, CA 94010. Custom Computer Software, Foster City, CA 94404. Department of Neurology, University of Texas-Southwestern Medical Center, Dallas, TX 75235.
Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin sheath of the CNS thought to be targeted by the autoimmune T cell response in multiple sclerosis (MS).
In this study, we have for the first time characterized the T cell epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC class II allele associated with MS in a subpopulation of patients.
Using MHC binding algorithms, we have predicted MOG peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG.
The data indicated that MOG peptide 97-108 (core 99-107, FFRDHSYQE) was the immunodominant HLA-DR4-restricted T cell epitope in vivo.
This peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic mice.
Interestingly, the same peptide was
presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a
role for the identified MOG epitopes in the pathogenesis of human MS.
PMID: 11739534 [PubMed - as supplied
PMID: 11739534 [PubMed - as supplied by publisher]