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

Bernhard Hemmer, Bruno Gran, Yingdong Zhao, Adriana Marques, Jeannick Pascal, Abraham Tzou, Takayuki Kondo, Irene Cortese, Bibiana Bielekova, Stephen E. Straus, Henry F. Mcfarland, Richard Houghten, Richard Simon, Clemencia Pinilla, Roland Martin

Research output: Contribution to journalArticlepeer-review

177 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1375-1382
Number of pages8
JournalNature Medicine
Issue number12
StatePublished - Dec 1999
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine


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