Genetic dissection of T cell receptor V beta 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 V beta subset(s) that initiates and/or perpetuates the antiislet response in a mouse model of spontaneous autoimmune diabetes (non-obese diabetic [NOD] mice). In studies reported here, we have bred NOD mice to a mouse strain that congenitally lacks approximately one-half of the conventional TCR V beta alleles. Included in this deletion are TCR V beta 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 V beta gene segments did not prevent the development of insulitis or diabetes.
Shizuru
J A
JA
Department of Medicine, Stanford University School of Medicine, California 94305.
Taylor-Edwards
C
C
Livingstone
A
A
Fathman
C G
CG
D000818:Animals; D002872:Chromosome Deletion; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005796:Genes; D006239:Haplotypes; D007116:Immunization, Passive; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta