A Model for the Evolution of the Mammalian T-cell Receptor α/δ and μ Loci Based on Evidence from the Duckbill Platypus

The specific recognition of antigen by T cells is critical to the generation of adaptive immune responses in vertebrates. T cells recognize antigen using a somatically diversified T-cell receptor (TCR). All jawed vertebrates use four TCR chains called alpha, beta, gamma, and delta, which are expressed as either a alpha beta or gamma delta heterodimer. Nonplacental mammals (monotremes and marsupials) are unusual in that their genomes encode a fifth TCR chain, called TCR mu, whose function is not known but is also somatically diversified like the conventional chains. The origins of TCR mu are also unclear, although it appears distantly related to TCR delta. Recent analysis of avian and amphibian genomes has provided insight into a model for understanding the evolution of the TCR delta genes in tetrapods that was not evident from humans, mice, or other commonly studied placental (eutherian) mammals. An analysis of the genes encoding the TCR delta chains in the duckbill platypus revealed the presence of a highly divergent variable (V) gene, indistinguishable from immunoglobulin heavy (IgH) chain V genes (VH) and related to V genes used in TCR mu. They are expressed as part of TCR delta repertoire (VH delta) and similar to what has been found in frogs and birds. This, however, is the first time a VH delta has been found in a mammal and provides a critical link in reconstructing the evolutionary history of TCR mu. The current structure of TCR delta and TCR mu genes in tetrapods suggests ancient and possibly recurring translocations of gene segments between the IgH and TCR delta genes, as well as translocations of TCR delta genes out of the TCR alpha/delta locus early in mammals, creating the TCR mu locus.