Broad, long-term objective: To ascertain the immunological importance of gammadelta T lymphocytes that recognize bacterial as well as self stress (heat shock) proteins.
Specific aims : 1. To further characterize an antigen that stimulates a major subset of murine gammadelta T cells. A subset of gammadelta T cell hybridomas derived from newborn thymus, all bearing similar receptors, are autoreactive when the cells are simply cultured by themselves in medium; all members of this group are further stimulated by mycobacterial antigen (PPD). A 17-amino acid synthetic peptide representing the mycobacterial homologue of HSP-60 strongly stimulates some of these hybridomas, but others only weakly. The corresponding peptide representing mouse HSP-60 is only weakly stimulatory for all of this subset. We will further investigate other related peptides for ability to stimulate those hybridomas. 2. To identify the molecule that acts to present peptides to these gammadelta cells. By isolating mutant hybridomas that no longer express surface Class I molecules, we will attempt to identify the presenter molecule for this subset of gammadelta cells. If it turns out that the presenter molecule is not beta-2 microglobulin associated, we will try to create presenter molecule minus mutants using a different selection technique. 3. To test tissues of the mouse for the presence of this subset of gammadelta cells, and to characterize their receptors and reactivity patterns for comparison to those from cells derived from newborn mouse thymus. We will characterize similar hybridomas derived from adult spleen, and search for such cells in other organs and tissues of the mouse. If cells of this subset are detected in other locations, we will also attempt a detailed characterization of some representative examples. 4. To examine the immunological role of this subset of gammadelta cells. We will immunize mice with Mycobacterium bovis BCG to see if cells from this subset become amplified, and if so, will examine the kinetics of their appearance. We will similarly study mice in which this gammadelta subset has been eliminated in order to determine if this subset aids in the immune defence against mycobacteria.
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| Roark, C E; Vollmer, M K; Cranfill, R L et al. (1993) Liver gamma delta T cells. TCR junctions reveal differences in heat shock protein-60-reactive cells in liver and spleen. J Immunol 150:4867-75 |
