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T cell receptor restriction of diabetogenic autoimmune NOD T cells.


ABSTRACT: 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.

SUBMITTER: Simone E 

PROVIDER: S-EPMC20120 | biostudies-literature | 1997 Mar

REPOSITORIES: biostudies-literature

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T cell receptor restriction of diabetogenic autoimmune NOD T cells.

Simone E E   Daniel D D   Schloot N N   Gottlieb P P   Babu S S   Kawasaki E E   Wegmann D D   Eisenbarth G S GS  

Proceedings of the National Academy of Sciences of the United States of America 19970301 6


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 clo  ...[more]

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