Bäckström B T, Milia E, Peter A, Jaureguiberry B, Baldari C T, Palmer E
Basel Institute for Immunology, Switzerland.
Immunity. 1996 Nov;5(5):437-47. doi: 10.1016/s1074-7613(00)80500-2.
Mutant alphabeta TCRs were generated by replacing domains of the alpha and beta chain constant regions with homologous domains from TCR delta and gamma chains, respectively. Chimeric TCRs in which the alpha chain contains TCR delta chain sequences within the connecting peptide domain are unresponsive to alloantigens and superantigens, and have defective interactions with the CD3/zeta complex. Although these antigen-unresponsive TCRs undergo zeta chain phosphorylation upon stimulation with superantigen, they do not generate a full signal capable of producing IL-2. Mutant TCRs acquire signaling activity with a combination of superantigen and calcium ionophore, indicating a defect in calcium-mediated signaling. Finally, a conserved motif, FETDxNLN, present in the alpha chain connecting peptide domain, is disrupted in all signaling-defective TCRs. This conserved alpha chain connecting peptide motif might mediate the transfer of signals from the alphabeta heterodimer to the CD3/zeta complex.
通过分别用TCRδ链和γ链的同源结构域替换α链和β链恒定区的结构域来生成突变型αβTCR。在连接肽结构域内α链包含TCRδ链序列的嵌合TCR对同种异体抗原和超抗原无反应，并且与CD3/ζ复合物的相互作用存在缺陷。尽管这些无抗原反应的TCR在用超抗原刺激后会发生ζ链磷酸化，但它们不会产生能够产生IL-2的完整信号。突变型TCR通过超抗原和钙离子载体的组合获得信号活性，表明钙介导的信号传导存在缺陷。最后，存在于α链连接肽结构域中的保守基序FETDxNLN在所有信号缺陷型TCR中均被破坏。这个保守的α链连接肽基序可能介导信号从αβ异二聚体传递到CD3/ζ复合物。
