grantor:
University of TorontoICA69 is a target autoantigen in type 1 diabetes. Our laboratory previously provided indirect evidence for antigenic mimicry between the ABBOS epitope of BSA and the Tep69 epitope of ICA69. We generated a NOD mouse T cell hybridoma, that recognizes both ABBOS and Tep69 and mapped the structural prerequisites of mimicry to the KAxyKK motif shared by both peptides. My data provide formal proof for antigenic mimicry between these two epitopes. To test the functional significance of Tep69-specific T cell pools, we used the adoptive transfer and the cyclophosphamide models of diabetes development. Intravenous administration of Tep69 into adoptive transfer recipients or NOD mice 5 days prior to cyclophosphamide (250mg/kg) dramatically precipitated the development of diabetes. My present data imply that Tep69-specific T cells can play a direct role in disease progression and suggests that caution should be used in designing antigen-based immunotherapeutic trials in humans.M.Sc
