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.

Project Start
1998-07-01
Project End
1999-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Jawaheer, Damini; Maranian, Paul; Park, Grace et al. (2010) Disease progression and treatment responses in a prospective DMARD-naive seropositive early rheumatoid arthritis cohort: does gender matter? J Rheumatol 37:2475-85
Ranganath, Veena K; Yoon, Jeonglim; Khanna, Dinesh et al. (2007) Comparison of composite measures of disease activity in an early seropositive rheumatoid arthritis cohort. Ann Rheum Dis 66:1633-40
Kahn, Katherine L; MacLean, Catherine H; Liu, Honghu et al. (2007) The complexity of care for patients with rheumatoid arthritis: metrics for better understanding chronic disease care. Med Care 45:55-65
Kahn, K L; Maclean, C H; Wong, A L et al. (2007) Assessment of American College of Rheumatology quality criteria for rheumatoid arthritis in a pre-quality criteria patient cohort. Arthritis Rheum 57:707-15
Kahn, K L; MacLean, C H; Liu, H et al. (2006) Application of explicit process of care measurement to rheumatoid arthritis: Moving from evidence to practice. Arthritis Rheum 55:884-91
Paulus, Harold E; Oh, MyungShin; Sharp, John T et al. (2004) Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal. Arthritis Rheum 50:1083-96
Liu, Honghu; Harker, Judith O; Wong, Andrew L et al. (2004) Case finding for population-based studies of rheumatoid arthritis: comparison of patient self-reported ACR criteria-based algorithms to physician-implicit review for diagnosis of rheumatoid arthritis. Semin Arthritis Rheum 33:302-10
Riemekasten, Gabriela; Langnickel, Dirk; Enghard, Philipp et al. (2004) Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells. J Immunol 173:5835-42
La Cava, Antonio; Ebling, Fanny M; Hahn, Bevra H (2004) Ig-reactive CD4+CD25+ T cells from tolerized (New Zealand Black x New Zealand White)F1 mice suppress in vitro production of antibodies to DNA. J Immunol 173:3542-8
Amjadi-Begvand, Sogol; Khanna, Dinesh; Park, Grace S et al. (2004) Dating the ""window of therapeutic opportunity"" in early rheumatoid arthritis: accuracy of patient recall of arthritis symptom onset. J Rheumatol 31:1686-92

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