The major objectives of our studies are to characterize cell surface structures on T lymphocytes and on accessory cells which play critical roles both in vivo and in vitro in the process of lymphocyte activation : 1) We have developed monoclonal antibodies (mAb) to a T lymphocyte activation antigen and demonstrated in biochemical studies that it is the vitronectin receptor (VNR) which is capable of interacting with the extracellular matrix (ECM) proteins -vitronectin, fibronectin, and fibrinogen. The VNR appears to play a critical role as an accessory molecule for a subpopulation of T cells which express the gamma/delta T cell receptor (TCR). Gamma/delta T cell lines and hybridomas which express the C(gamma)4, V(delta)6 chains appear to recognize an autoantigen; however, activation of these lines requires that, in addition, to engagement of the TCR by antigen, the VNR must also bind to its ligand on ECM-proteins. 2) We cloned a cDNA for a cell surface disulfide linked 44 kD dimer (Ly-49) which is a member of a large multigene family and which is expressed on rare T cell tumors. We have mapped the gene which encodes this antigen to the short arm of mouse chromosome 6 near the gene which encodes the murine natural killer (NK) cell marker, NK1.1. Ly-49 also may play a role in NK cell function because 30% of highly purified NK cells express Ly-49; it is also possible that NK1.1 is a member of the Ly-49 multigene family. 3) In continuing studies of cell surface antigens which are coupled to the membrane via a phosphatidylinositol (PI) linkage, we have shown that mAbs to the human CD59 antigen are capable of inducing human T cell proliferation and cytokine production in the presence of phorbol ester and a crosslinking second antibody. 4) In order to probe the cellular mechanisms whereby the administration of the immunosuppressive drug, Cyclosporine A (CsA) induces autoimmune disease, we have established a model in which autoantibodies to gastric mucosal antigens can be induced in the offspring of mothers treated only during pregnancy with CsA.
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