Lime borreliosis is the most common arthropod-borne infection in the United States and causes significant and prolonged morbidity in many individuals. The diagnosis, treatment and prevention of this disease has become a focus of intense current interest. Human T and B cell immune responses to the etiological agent, B. burgdorferi (Bb), can now be readily measured in vitro and applying newer techniques of cellular immunology and molecular biology will allow the precise characterization of immune responses to this bacteria. Defining T and B cell immunodominant epitopes, delineating the nature of lymphokine production by immune T cells, and clarifying the mechanisms by which specific T cells support anti-Bb antibody secretion by different classes of B cells (e.g., IgG, and IgG2) will provide important insights into both disease mechanisms and prevention through vaccines and impact on our understanding of human immune responses in general.
Our specific aims are to: 1. Characterize Bb-specific T cell responses by: a) using limiting dilutions experiments aimed at profiling functional capabilities of individual Bb-specific T cells; b) using T cell immunoblots, isolated proteins and peptides to map T cell stimulatory epitopes and define cross-reactive epitopes between other spirochetes; c) developing Bb-specific T cell lines and clones to address the same questions more precisely and using them to detect cross-reactivity to related self antigens; and d) defining the relationship between epitope recognition and MHC restriction for these Bb determinants. 2. Characterize Bb-specific B cell responses by: a) using in vitro generated antibody (stimulated by both PWM and Bb) to determine early B cell immunodominant determinants; b) using specific lymphokine and lymphokine combinations to include anti-Bb production in different classes of B cells; c) using defined T cell clones to establish the requirements for T-B collaboration in defined populations of B cells; and d) determining if seronegative, but chronically infected individuals lack either the B cell or T cell helper arm of the anti-Bb response. 3. Pursue other, less major aims by: a) using Bb-specific antibodies directed against peptidogylan-polysaccharide polymers to detect Bb antigens in patient Derived fluids; b) using HTLV-I to transform novel lymphokine producing T cell lines or clones to construct cell lines constitutively secreting these lymphokines.
| Volkman, D J; Luft, B J; Gorevic, P D et al. (1991) Characterization of an immunoreactive 93-kDa core protein of Borrelia burgdorferi with a human IgG monoclonal antibody. J Immunol 146:3177-82 |
