Virus-induced diabetes in a transgenic model: Role of cross-reacting viruses and quantitation of effector T cells needed to cause disease

Virus-specific cytotoxic T lymphocytes (CTL) at frequencies of >1/1,000 are sufficient to cause insulin-dependent diabetes mellitus (IDDM) in transgen ic mice whose pancreatic beta cells express as "self'" antigen a protein fr om a virus later used to initiate infection. The inability to generate suff icient effector CTL for other cross-reacting viruses that fail to cause IDD M could be mapped to point mutations in the CTL epitope or its COO- flankin g region. These data indicate that IDDM and likely other autoimmune disease s are caused by a quantifiable number of T cells, that neither standard epi demiologic markers nor molecular analysis with nucleic acid probes reliably distinguishes between viruses that do or do not cause; diabetes, and that a single-amino-acid change flanking a CTL epitope can interfere with antige n presentation and development of autoimmune disease in vivo.