The molecular assembly of the marsupial γμ 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.

Automated summary

The study describes a unique population of γμTCRs found exclusively in non-eutherian mammals, with restricted diversity in the Vγ and Vμj domains and highly diverse unpaired Vμ domain. Crystal structures of two distinct γμTCRs reveal the structural basis of the association and suggest a major antigen recognition determinant in the CDR3μ loop of the Vμ domain. This defines the molecular basis underlying the assembly of a third TCR lineage, the γμTCR.