The specific aim of this proposal is to dissect the T-cell receptor (TCR) repertoire of autoimmune ear disease (AED). We will test if the following hypotheses will apply. 1. T-cells are the key factors in mediating AED and therefore AED can be transferrable by cell transfer to naive syngeneic mice. 2. TCR usage in mice is restricted so that limited numbers of Valpha and Vbeta gene segments are used in AED. 3. If such specific TCR V segment usage in AED is identified, therapies using either antibodies against these TCRs or peptides from Vbeta CDR2 sequence may be used to abrogate the small population of T-cells that can cause AED. To investigate the above specific aims, we will (1) produce a series of ear disease inducing T-cell lines and T-cell hybridomas (made from disease inducing T-cell) specific to collagen and peptides (epitope containing). (2) We will determine the DNA structures of the TCR gene and TCR gene usage in ear tissue will also be examined. (3) Antibodies will be used to block these TCRs. (4) Also, peptides of the GDR2 region of Valpha and Vbeta will be synthesized to inhibit the T-cell response to antigen in vitro.
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