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Infection and Immunity, January 2007, p. 243-251, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01110-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cerebrospinal Fluid-Infiltrating CD4+ T Cells Recognize Borrelia burgdorferi Lysine-Enriched Protein Domains and Central Nervous System Autoantigens in Early Lyme Encephalitis{triangledown}

Jan D. Lünemann,1,5 Harald Gelderblom,1,6 Mireia Sospedra,1,2 Jacqueline A. Quandt,1 Clemencia Pinilla,3 Adriana Marques,4 and Roland Martin1,2*

Neuroimmunology Branch, Cellular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892,1 Institute for Neuroimmunology and Clinical MS Research (INiMS), Center for Molecular Neurobiology Hamburg (ZMNH), University Clinic Eppendorf, Falkenried 94, 20251 Hamburg, Germany,2 Mixture Science and Torrey Pines Institute for Molecular Studies, San Diego, California 92121,3 Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,4 Laboratory of Viral Immunobiology, The Rockefeller University, New York, New York 10021,5 Department of Neurology and Psychiatry, Charité Medical Center, Humboldt University, 10098 Berlin, Germany6

Received 14 July 2006/ Returned for modification 15 September 2006/ Accepted 10 October 2006

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.

* Corresponding author. Mailing address: Institute for Neuroimmunology and Clinical MS Research (INiMS), Center for Molecular Neurobiology Hamburg (ZMNH), University Clinic Eppendorf, Falkenried 94, 20251 Hamburg, Germany. Phone: 49 40 42803 6273. Fax: 49 40 42803 4772. E-mail: roland.martin{at}zmnh.uni-hamburg.de.

{triangledown} Published ahead of print on 23 October 2006.

Editor: J. L. Flynn

Infection and Immunity, January 2007, p. 243-251, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01110-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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