The Molecular Assembly Of The Marsupial Gamma Mu T Cell Receptor Defines A Third T Cell Lineage

a beta and gamma delta T cell receptors (TCRs) are highly diverse antigen receptors that define two evolutionarily conserved T cell lineages. We describe a population of gamma mu TCRs found exclusively in non-eutherian mammals that consist of a two-domain (V gamma-C gamma) gamma-chain paired to a three-domain (V mu-V mu j-C mu) mu-chain. gamma mu TCRs were characterized by restricted diversity in the V gamma and V mu j domains and a highly diverse unpaired V mu domain. Crystal structures of two distinct gamma mu TCRs revealed the structural basis of the association of the gamma mu TCR heterodimer. The Vm domain shared the characteristics of a single-domain antibody within which the hypervariable CDR3 mu loop suggests a major antigen recognition determinant. We define here the molecular basis underpinning the assembly of a third TCR lineage, the gamma mu TCR.