title: Identification of an epitope derived from human proteolipid protein that can induce autoreactive CD8+ cytotoxic T lymphocytes restricted by HLA-A3: evidence for cross-reactivity with an environmental microorganism.
abstract: The demyelination process that occurs in the central nervous system (CNS) of patients with multiple sclerosis (MS) is in part due to an inflammatory response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter. In this study, we have identified a peptide sequence derived from the CNS-specific myelin protein proteolipid protein (PLP) which could bind to HLA-A3 and induce a HLA-A3-restricted CD8+ CTL response from HLA-A3+ donors. These PLP peptide-specific CTL could lyse HLA-A3+ target cells pulsed with a homologous peptide derived from the CRM1 protein of Saccharomyces cerevisae. These findings demonstrate the immunogenic potential of a PLP-derived peptide for generation of autoreactive HLA-A3-restricted CD8+ CTL, and further show that these CTL can be activated by a peptide derived from a common environmental microorganism.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
authors.forename: K
authors.initials: K
authors.lastname: Honma
authors.forename: K C
authors.initials: KC
authors.lastname: Parker
authors.forename: K G
authors.initials: KG
authors.lastname: Becker
authors.forename: H F
authors.initials: HF
authors.lastname: McFarland
authors.forename: J E
authors.initials: JE
authors.lastname: Coligan
authors.forename: W E
authors.initials: WE
authors.lastname: Biddison
mesh_terms: D000328:Adult; D001059:Apoproteins / Q000276:immunology*; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D015791:HLA-A3 Antigen / Q000276:immunology*; D006801:Humans; D028884:Karyopherins; D008297:Male; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097606:Exportin 1 Protein
chemical_list: D001059:Apoproteins; D016207:Cytokines; D000939:Epitopes; D005656:Fungal Proteins; D015791:HLA-A3 Antigen; D028884:Karyopherins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein