Molecular Anatomy and Number of Antigen Specific CD8 T Cells Required to Cause Type 1 Diabetes

We quantified cd8 t cells needed to cause type 1 diabetes and studied the anatomy of the cd8 t cell/beta (β) cell interaction at the immunologic synapse. we used a transgenic model,in situ tetramer staining to distinguish antigen specific cd8 t cells from total t cells infiltrating islets and a variety of viral mutants selected for functional deletion(s) of various cd8 t cell epitopes. twenty percent of cd8 t cells in the spleen were specific for all immunodominant and subdominant viral glycoprotein (gp) epitopes. ctls to the immunodominant lcmv gp33-41 epitope accounted for 63% of the total (12.5% of tetramers). in situ hybridization analysis demonstrated only 1 to 2% of total infiltrating cd8 t cells were specific for gp33 cd8 t cell epitope,yet diabetes occurred in 94% of mice. the immunologic synapse between gp33 cd8 ctl and β cell contained lfa-1 and perforin. silencing both immunodominant epitopes (gp33,gp276-286) in the infecting virus led to a four-fold reduction in viral specific cd8 ctl responses,negligible lymphocyte infiltration into islets and absence of diabetes.