Platypus TCRμ Provides Insight into the Origins and Evolution of a Uniquely Mammalian TCR Locus

TCR mu is an unconventional TCR that was first discovered in marsupials and appears to be absent from placental mammals and nonmammals. In this study, we show that TCRm is also present in the duckbill platypus, an egg-laying monotreme, consistent with TCR mu being ancient and present in the last common ancestor of all extant mammals. As in marsupials, platypus TCR mu is expressed in a form containing double V domains. These V domains more closely resemble Ab V than that of conventional TCR. Platypus TCR mu differs from its marsupial homolog by requiring two rounds of somatic DNA recombination to assemble both Vexons and has a genomic organization resembling the likely ancestral form of the receptor genes. These results demonstrate that the ancestors of placental mammals would have had TCRm but it has been lost from this lineage. The Journal of Immunology, 2011, 187: 5246-5254.