Evolution of T cell receptor (TCR) αβ heterodimer assembly with the CD3 complex

Abstract

T cell antigen receptors (TCR) are composed of an antigen-recognizing unit, the TCRαβ heterodimer, and a signal transduction ensemble, the CD3 complex. Whereas mammals possess three CD3 dimers (δε, γε, and ζ2), birds and amphibians have only two (δ/γ-ε and ζ2). To understand evolutionary changes in TCR/CD3 assembly, a phylogenetic approach was employed to dissect the interaction of TCRαβ heterodimers with the CD3 components. While sheep and mouse TCRα and TCRβ chains could replace the corresponding human chains in mutant human T cells to restore surface TCR/CD3 expression and function, chicken TCRα, TCRβ and CD3δ/γ 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 TCRαβ heterodimers and the human CD3 complex. In contrast, if no CD3 molecules are present (non-T cells), TCRα-TCRβ 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 CD3γ and CD3δ genes from a single prototypic chicken δ/γ gene. Our data suggest that the structures in mammalian TCR.C regions, which distinguish between CD3δ and CD3γ chains, have evolved with the appearance of two separate CD3δ and CD3γ functions.