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

Elucidating the cellular immune response to infectious agents is a prerequi site for understanding disease pathogenesis and designing effective vaccine s. 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 dama ge may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively iden tify both microbial epitopes and candidate autoantigens. The approach combi nes data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patien t with chronic neuroborreliosis, we show that this strategy leads to the id entification of potentially relevant T-cell targets derived from both Borre lia 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 preferential ly recognize different peptides derived from the same organism, thus demons trating that flexibility in T-cell recognition does not preclude specificit y. This approach has potential applications in the identification of ligand s in infectious diseases, tumors and autoimmune diseases.