T cell receptor restriction of diabetogenic autoimmune NOD T cells.
Restricted use of T cell receptor (TCR) gene segments is characteristic of several induced autoimmune disease models. TCR sequences have previously been unavailable for pathogenic T cells which react with a defined autoantigen in a spontaneous autoimmune disease. The majority of T cell clones, derived from islets of NOD mice which spontaneously develop type I diabetes, react with insulin peptide B-(9-23). We have sequenced the alpha and beta chains of TCRs from these B-(9-23)-reactive T cell clones. No TCR beta chain restriction was found. In contrast, the clones (10 of 13) used V alpha13 coupled with one of two homologous J alpha segments (J alpha45 or J alpha34 in 8 of 13 clones). Furthermore, 9 of 10 of the V alpha13 segments are a novel NOD sequence that we have tentatively termed V alpha13.3. This dramatic alpha chain restriction, similar to the beta chain restriction of other autoimmune models, provides a target for diagnostics and immunomodulatory therapy.
Simone
E
E
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA.
Daniel
D
D
Schloot
N
N
Gottlieb
P
P
Babu
S
S
Kawasaki
E
E
Wegmann
D
D
Eisenbarth
G S
GS
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D007328:Insulin; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta