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Article
Nature Medicine  5, 1375 - 1382 (1999)
doi:10.1038/70946

Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease

Bernhard Hemmer1, 5, 6, Bruno Gran1, 6, Yingdong Zhao2, Adriana Marques3, Jeannick Pascal4, Abraham Tzou1, Takayuki Kondo1, Irene Cortese1, Bibiana Bielekova1, Stephen E. Straus3, Henry F. McFarland1, Richard Houghten4, Richard Simon2, Clemencia Pinilla4 & Roland Martin1

1  Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5B-16, 10 Center DR MSC 1400, Bethesda, Maryland 20892-1400, USA

2  Biometric Research Branch, National Cancer Institute, National Institutes of Health, 6130 Executive Boulevard, EPN 739, Rockville, Maryland 20854, USA

3  Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N-228, 10 Center DR MSC 1888, Bethesda, Maryland 20892-1888, USA

4  Mixture Sciences, and Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego , California, 92121, USA

5  Department of Neurology, University of Marburg, Rudolf Bultmann-Str. 8, 35039 Marburg, Germany

6  B.H. and B.G. contributed equally to this study.

Correspondence should be addressed to Clemencia Pinilla pinilla@tpims.org or Roland Martin Roland_Martin@nih.gov
Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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