Open AccessCerebrospinal Fluid-Infiltrating CD4+T Cells RecognizeBorrelia burgdorferiLysine-Enriched Protein Domains and Central Nervous System Autoantigens in Early Lyme Encephalitis
Author(s) -
Jan D. Lünemann,
Hans Gelderblom,
Mireia Sospedra,
Jacqueline A. Quandt,
Clemencia Pinilla,
Adriana Marques,
Roland Martin
Publication year - 2007
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01110-06
Subject(s) - borrelia burgdorferi , biology , epitope , neuroborreliosis , spirochaetaceae , lyme disease , myelin basic protein , t cell , antigen , immunology , virology , central nervous system , myelin , antibody , immune system , neuroscience
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 toBorrelia burgdorferi lysate were present in the CSF of a patient with acute Lyme encephalitis. Some T-cell clones recognized previously uncharacterizedB. 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 byB. burgdorferi -specific T cells is not restricted to chronic and treatment-resistant manifestations.