The identification of T cell recognition of lipid and lipoglycan antigens presented by CD1 challenges the existing paradigm that non peptide antigens stimulate antigen-specific responses from B cells only. Staphylococci produce non peptide molecules, such as polysaccharide capsules and lipoteichoic acid (LTA), which are targets of the humoral immune response and critical to disease pathogenesis. We believe that T- cell recognition of these non peptides is central to host immunity to staphylococcal infections. We propose to investigate the CD1-mediated antigen presentation pathway to staphylococci. In the first phase of this project we will derive CD1-restricted T cell lines from the blood of healthy donors as well as from the synovial fluid, synovium, and blood of septic arthritis patients to determine their CD1 restriction. Second, we will determine the antigen reactivity of these CD1-restricted T-cells using fractionated bacterial extracts and purified antigens. Third, we will determine the immunologic function of the staphylococcal-reactive CD1-restricted T-cells by measuring their cytokine patterns and the cytotoxicity of co-cultured infected macrophages. We hypothesize that CD1- restricted T-cells recognizing staphylococcal antigens will differ in the synovial fluid and synovia of patients with staphylococcal arthritis, compared to their blood and the blood of healthy individuals. Differences may be found in the frequency and/or function of CD1-restricted T-cells. Our preliminary data suggest that CD1 APC and CD1-restricted T-cells can be recovered from inflammatory synovial fluids. Finally, the CD1 system is distinct in several ways from the MHC systems, in its tissue distribution, gene regulation, and nature of antigens presented, and thus is likely to perform unique immunological functions that extend of complement those performed by the MHC.
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