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The molecular assembly of the marsupial γμ T cell receptor defines a third T cell lineage

Kimberly A Morrissey1, Marcin Wegrecki2, T Praveena2,3

  • 1Department of Biology, Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, NM, USA.

Science (New York, N.Y.)
|March 26, 2021
PubMed

αβ and γδ T cell receptors (TCRs) are highly diverse antigen receptors that define two evolutionarily conserved T cell lineages. We describe a population of γμTCRs found exclusively in non-eutherian mammals that consist of a two-domain (Vγ-Cγ) γ-chain paired to a three-domain (Vμ-Vμj-Cμ) μ-chain. γμTCRs were characterized by restricted diversity in the Vγ and Vμj domains and a highly diverse unpaired Vμ domain. Crystal structures of two distinct γμTCRs revealed the structural basis of the association of the γμTCR heterodimer. The Vμ domain shared the characteristics of a single-domain antibody within which the hypervariable CDR3μ loop suggests a major antigen recognition determinant. We define here the molecular basis underpinning the assembly of a third TCR lineage, the γμTCR.

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