Gouaillard C, Huchenq-Champagne A, Arnaud J, Chen Cl C L, Rubin B
Unité de Physiopathologie Cellulaire et Moléculaire (UPCM), CNRS UPR-2163, CHU de Purpan, Toulouse, France.
Eur J Immunol. 2001 Dec;31(12):3798-805. doi: 10.1002/1521-4141(200112)31:12<3798::aid-immu3798>3.0.co;2-z.
T cell antigen receptors (TCR) are composed of an antigen-recognizing unit, the TCRalpha beta heterodimer, and a signal transduction ensemble, the CD3 complex. Whereas mammals possess three CD3 dimers (delta epsilon, gamma epsilon, and zeta2), birds and amphibians have only two (delta/gamma-epsilon and zeta2). To understand evolutionary changes in TCR/CD3 assembly,a phylogenetic approach was employed to dissect the interaction of TCRalpha beta heterodimers with the CD3 components. While sheep and mouse TCRalpha and TCRbeta chains could replace the corresponding human chains in mutant human T cells to restore surface TCR/CD3 expression and function, chicken TCRalpha, TCRbeta and CD3delta/gamma chains were unable to replace the corresponding human chains in forming a chimeric TCR/CD3 complex. The inability of chicken TCR/CD3 components to replace the human molecules in T cells was found to result from the lack of interaction between chicken TCRalpha beta heterodimers and the human CD3 complex. In contrast, if no CD3 molecules are present (non-T cells), TCRalpha -TCRbeta chain pairing can take place in an apparently non-controlled way. Thus, the TCR-CD3 interactions have changed with the evolutionary divergence of two mammalian CD3gamma and CD3delta genes from a single prototypic chicken delta/gamma gene. Our data suggest that the structures in mammalian TCR.C regions, which distinguish between CD3delta and CD3gamma chains, have evolved with the appearance of two separate CD3delta and CD3gamma functions.
T细胞抗原受体（TCR）由一个抗原识别单位，即TCRαβ异二聚体，和一个信号转导组件，即CD3复合体组成。哺乳动物拥有三种CD3二聚体（δε、γε和ζ2），而鸟类和两栖动物只有两种（δ/γ-ε和ζ2）。为了了解TCR/CD3组装过程中的进化变化，我们采用了系统发育方法来剖析TCRαβ异二聚体与CD3组分之间的相互作用。虽然绵羊和小鼠的TCRα和TCRβ链可以替代突变型人类T细胞中的相应人类链，以恢复表面TCR/CD3的表达和功能，但鸡的TCRα、TCRβ和CD3δ/γ链无法替代相应的人类链来形成嵌合TCR/CD3复合体。研究发现，鸡的TCR/CD3组分无法在T细胞中替代人类分子，是由于鸡的TCRαβ异二聚体与人类CD3复合体之间缺乏相互作用。相反，如果不存在CD3分子（非T细胞），TCRα - TCRβ链配对可能会以一种明显不受控制的方式发生。因此，随着两个哺乳动物CD3γ和CD3δ基因从单一的原型鸡δ/γ基因进化分化，TCR - CD3相互作用也发生了变化。我们的数据表明，哺乳动物TCR.C区域中区分CD3δ和CD3γ链的结构，是随着两种独立的CD3δ和CD3γ功能的出现而进化的。
