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Analysis of T cell receptor beta chains that combine with dominant conserved TRAV5D-4*04 anti-insulin B:9-23 alpha chains.


ABSTRACT: The objective of this study was to define the spectrum of TCR beta chains permissive for T cells with alpha chains containing the conserved TRAV5D-4*04 sequence to target the insulin B:9-23 peptide, a major epitope for initiation of diabetes in the NOD mouse.We produced T cell hybridomas from mice with single T cell receptors (BDC12-4.1 TCR alpha(+)beta(+) double transgenic mice and BDC12-4.4 TCR alpha(+)beta(+) double retrogenic mice) or from mice with only the corresponding alpha chains transgene or retrogene and multiple endogenous TCR beta chains.Hybridomas with the complete BDC12-4.1 and BDC12-4.4 T cell receptors, despite having markedly different TCR beta chains, responded to similar B:9-23 peptides. Approximately 1% of the hybridomas from mice with the fixed TRAV5D-4*04 alpha chains and multiple endogenous beta chains responded to B:9-23 peptides while the majority of hybridomas with different beta chains did not respond. There was no apparent conservation of TCR beta chain sequences in the responding hybridomas.Approximately 1% of hybridomas utilizing different TCR beta chains paired with the conserved TRAV5D-4*04 containing alpha chains respond to insulin peptide B:9-23. Therefore, TCR beta chain sequences make an important contribution to insulin B:9-23 peptide recognition but multiple beta chain sequences are permissive for recognition.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC4383244 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Analysis of T cell receptor beta chains that combine with dominant conserved TRAV5D-4*04 anti-insulin B:9-23 alpha chains.

Zhang Li L   Jasinski Jean M JM   Kobayashi Masakazu M   Davenport Bennett B   Johnson Kelly K   Davidson Howard H   Nakayama Maki M   Haskins Kathryn K   Eisenbarth George S GS  

Journal of autoimmunity 20090316 1


<h4>Objective</h4>The objective of this study was to define the spectrum of TCR beta chains permissive for T cells with alpha chains containing the conserved TRAV5D-4*04 sequence to target the insulin B:9-23 peptide, a major epitope for initiation of diabetes in the NOD mouse.<h4>Materials and methods</h4>We produced T cell hybridomas from mice with single T cell receptors (BDC12-4.1 TCR alpha(+)beta(+) double transgenic mice and BDC12-4.4 TCR alpha(+)beta(+) double retrogenic mice) or from mice  ...[more]

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