Epitopes described in "Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129-specific humanized TCR transgenic mice."

Article Authors:Jacqueline A Quandt; Mirza Baig; Karen Yao; Kazuyuki Kawamura; Jaebong Huh; Samuel K Ludwin; Hong-Jin Bian; Mark Bryant; Laura Quigley; Zoltan A Nagy; Henry F McFarland; Paolo A Muraro; Roland Martin; Kouichi Ito
Article Title:Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129-specific humanized TCR transgenic mice.
Reference Detail
Reference ID:365
Abstract:Amino acid residues 111-129 represent an immunodominant epitope of myelin basic protein (MBP) in humans with human leukocyte antigen (HLA)-DRB1*0401 allele(s). The MBP 111-129-specific T cell clone MS2-3C8 was repeatedly isolated from a patient with multiple sclerosis (MS), suggesting an involvement of MS2-3C8 T cells in the pathogenesis. To address the pathogenic potential of the MS2-3C8 T cell clone, we generated transgenic (Tg) mice expressing its T cell receptor and restriction element, HLA-DRB1*0401, to examine the pathogenic characteristics of MS2-3C8 Tg T cells by adoptive transfer into HLA-DRB1*0401 Tg mice. In addition to the ascending paralysis typical of experimental autoimmune encephalomyelitis, mice displayed dysphagia due to restriction in jaw and tongue movements and abnormal gait. In accordance with the clinical phenotype, infiltrates of MS2-3C8 Tg T cells and inflammatory lesions were predominantly located in the brainstem and the cranial nerve roots in addition to the spinal cord and spinal nerve roots. Together, these data suggest a pathogenic role of MBP-specific T cells in inflammatory demyelination within the brainstem and cranial nerve roots during the progression of MS. This notion may help to explain the clinical and pathological heterogeneity of MS.
Affiliations:Department of Neurology, Robert Wood Johnson Medical School, UMDNJ, 683 Hoes Ln., Piscataway, NJ 08854, USA.
Reference Type:Literature
PubMed ID:15263029
Journal:J Exp Med
Journal Volume:200
Article Pages:223-34
Journal ISSN:0022-1007
Article Chemical List:Cytokines;HLA-DR Antigens;HLA-DRB1 Chains;HLA-DRB1*04:01 antigen;Receptors, Antigen, T-Cell
Article MeSH List:Amino Acid Sequence; Animals; Cell Separation; Cytokines(biosynthesis); Disease Models, Animal; Disease Progression; Encephalomyelitis, Autoimmune, Experimental(metabolism); Flow Cytometry; HLA-DR Antigens(metabolism); HLA-DRB1 Chains; Humans; Immunohistochemistry; Inflammation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Multiple Sclerosis(metabolism); Phenotype; Receptors, Antigen, T-Cell(genetics; metabolism); Time Factors
Curation Last Updated:2015-06-05 00:10:16