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

Area of Science:

• Immunology
• Evolutionary Biology
• Molecular Biology

Background:

• T cell receptors (TCRs) mediate adaptive immunity by recognizing antigens.
• The TCR complex consists of the antigen-binding TCRalpha beta heterodimer and the signal-transducing CD3 complex.
• Mammals have three CD3 dimers, while birds and amphibians have two, suggesting evolutionary divergence.

Purpose of the Study:

• To investigate the evolutionary changes in TCR/CD3 complex assembly using a phylogenetic approach.
• To dissect the interactions between TCRalpha beta heterodimers and CD3 components across different species.

Main Methods:

• Phylogenetic analysis of TCR/CD3 components.
• Functional assays using mutant human T cells and chimeric TCR/CD3 complexes.
• Investigating TCRalpha-TCRbeta chain pairing in non-T cells.

Main Results:

• Sheep and mouse TCR chains functionally replaced human counterparts in mutant T cells.
• Chicken TCRalpha, TCRbeta, and CD3delta/gamma chains could not replace human chains, indicating a lack of interaction.
• Chicken TCRalpha beta heterodimers failed to interact with the human CD3 complex.
• TCRalpha-TCRbeta chain pairing occurred without CD3 molecules in non-T cells.

Conclusions:

• TCR-CD3 interactions have evolved with the divergence of mammalian CD3gamma and CD3delta genes from a single ancestral gene.
• Mammalian TCR.C regions evolved structures to differentiate between CD3delta and CD3gamma chains, enabling distinct functions.