Zhang Li, Jasinski Jean M, Kobayashi Masakazu, Davenport Bennett, Johnson Kelly, Davidson Howard, Nakayama Maki, Haskins Kathryn, Eisenbarth George S
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
J Autoimmun. 2009 Aug;33(1):42-9. doi: 10.1016/j.jaut.2009.02.003. Epub 2009 Mar 16.
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.
本研究的目的是确定允许T细胞的TCRβ链谱，这些T细胞的α链含有保守的TRAV5D-4*04序列，以靶向胰岛素B:9-23肽，这是NOD小鼠糖尿病发病的主要表位。
我们从小鼠制备T细胞杂交瘤，这些小鼠具有单一T细胞受体（BDC12-4.1 TCRα(+)β(+)双转基因小鼠和BDC12-4.4 TCRα(+)β(+)双逆转基因小鼠），或者仅具有相应的α链转基因或逆转基因以及多个内源性TCRβ链。
具有完整BDC12-4.1和BDC12-4.4 T细胞受体的杂交瘤，尽管具有明显不同的TCRβ链，但对相似的B:9-23肽有反应。来自具有固定TRAV5D-4*04α链和多个内源性β链的小鼠的杂交瘤中，约1%对B:9-23肽有反应，而大多数具有不同β链的杂交瘤无反应。在有反应的杂交瘤中，TCRβ链序列没有明显的保守性。
约1%利用不同TCRβ链与含保守TRAV5D-4*04的α链配对的杂交瘤对胰岛素肽B:9-23有反应。因此，TCRβ链序列对胰岛素B:9-23肽的识别有重要贡献，但多个β链序列都允许识别。
