Genetic Dissection of T Cell Receptor Vf 3 Gene Requirements for Spontaneous Murine Diabetes

It has been demonstrated, in certain autoimmune disease models, that pathogenic T cells express antigen receptors of limited diversity. It has been suggested that the T cells responsible for the pathogenesis of type I diabetes mellitus might similarly demonstrate restricted T cell receptor (TCR) usage . Recently, attempts have been made to identify the Va subset(s) that initiates and/or perpetuates the andislet response in a mouse model of spontaneous autoimmune diabetes (nonobese diabetic [NOD] mice) . In studies reported here, we have bred NOD mice to a mouse strain that congenitally lacks approximately one-halfof the conventional TCR V/3 alleles. Included in this deletion are TCR V0 gene products previously implicated as being involved in the pathogenesis of NOD disease . By studying second backcross-intercross animals, we were able to demonstrate that this deletion of TCR V0 gene segments did not prevent the development of insulitis or diabetes .