The present proposal aims to understand OspA-mediated adherence of spirochete Borrelia burgdorferi during Lyme disease. B. burgdorferi cycles between an arthropod vector and a mammalian host in nature and transmitted to humans by the bite of an infected Ixodes scapularis tick. Outer surface protein A, a lipoprotein found on the surface of the bacterium, forms the basis of the recombinant human vaccine against Lyme disease. Differential expression of ospA during life cycle of the spirochete indicates the important temporal and tissue-specific function of the protein by B. burgdorferi in the tick gut. Our preliminary data now show that OspA mediates B. Burgdorferi attachment to tick gut via binding to a tick gut protein. In the present study we will characterize OspA binding to the tick gut, including the identification of OspA epitopes that facilitate this interaction. Then we will identify and clone the tick receptor for OspA. Since OspA is also expressed sometimes during late stages of arthritis, we will also seek to test whether OspA mediates B. Burgdorferi adherence in the joints. These studies should provide new knowledge that may be useful for developing an alternate OspA or OspA-receptor based Lyme disease vaccine and also to understand pathogenesis of Lyme disease.