title: Cerebrospinal fluid-infiltrating CD4+ T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early lyme encephalitis.
abstract: Neurological manifestations of Lyme disease are usually accompanied by inflammatory changes in the cerebrospinal fluid (CSF) and the recruitment of activated T cells into the CSF compartment. In order to characterize the phenotype and identify target antigens of CSF-infiltrating T cells in early neuroborreliosis with central nervous system (CNS) involvement, we combined T-cell cloning, functional testing of T-cell responses with positional scanning synthetic combinatorial peptide libraries, and biometric data analysis. We demonstrate that CD4+ gamma interferon-producing T cells specifically responding to Borrelia burgdorferi lysate were present in the CSF of a patient with acute Lyme encephalitis. Some T-cell clones recognized previously uncharacterized B. burgdorferi epitopes which show a specific enrichment for lysine, such as the heat shock-induced chaperone HSP90. Degenerate T-cell recognition that included T-cell responses to borrelia-specific and CNS-specific autoantigens derived from the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) could be demonstrated for one representative clone. Our results show that spirochetal antigen-specific and Th1-polarized CD4+ lymphocytes infiltrate the CSF during monophasic CNS symptoms of Lyme disease and demonstrate that cross-recognition of CNS antigens by B. burgdorferi-specific T cells is not restricted to chronic and treatment-resistant manifestations.
authors.affiliation: Neuroimmunology Branch, Cellular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Lünemann
authors.forename: Harald
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Mireia
authors.initials: M
authors.lastname: Sospedra
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Quandt
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.forename: Adriana
authors.initials: A
authors.lastname: Marques
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology*; D002999:Clone Cells; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D020852:Lyme Neuroborreliosis / Q000276:immunology*; D008239:Lysine; D008297:Male; D008875:Middle Aged; D019151:Peptide Library
chemical_list: D000942:Antigens, Bacterial; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D018841:HSP90 Heat-Shock Proteins; D019151:Peptide Library; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D008239:Lysine