Cerebrospinal fluid-infiltrating CD4+ T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early lyme encephalitis.
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.
Lünemann
Jan D
JD
Neuroimmunology Branch, Cellular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gelderblom
Harald
H
Sospedra
Mireia
M
Quandt
Jacqueline A
JA
Pinilla
Clemencia
C
Marques
Adriana
A
Martin
Roland
R
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
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