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J Autoimmun. 2009 Aug;33(1):42-9. doi: 10.1016/j.jaut.2009.02.003. Epub 2009 Mar 16.

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

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  • 1Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.

Abstract

OBJECTIVE:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
19286348
[PubMed - indexed for MEDLINE]
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