Compositions and methods are provided for detection, diagnosis and prognosis of
Lyme disease (LD), including a method for confirming Borrelia spp. infection by contacting,
in vitro,
whole blood samples from subjects suspected of having LD with synthetic peptides comprising T-
cell epitope-containing regions derived from Borrelia proteins that are expressed at different stages of
Lyme disease, and indirectly detecting LD-specific activated T-cells by determining production of a T-
cell immune response indicator (e.g.,
interferon-Y) in response to stimulation by the peptides. Also disclosed are methods for predicting
elimination of LD spirochetes in LD patients who have undergone LD treatment, by exposing
whole blood samples from such subjects to peptides comprising specific T-
cell epitope regions of Borrelia proteins that are expressed at different stages of
Lyme disease, and confirming a lack of Borrelia-specific activated T-cells in the samples by the absence of a detectable T-
cell immune response indicator (e.g.,
interferon-Y).