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

Abstract

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.

Hello Possums!

“…To define the architecture of a TCR containing TCRμ, Morrissey et al 2 . set about determining which TCR chain pairs with TCRμ with a single‐cell transcriptome RNA sequencing campaign.…”

“…1 This chain, termed TCRl, had a constant (Cl) and variable (Vl) domain like other TCR chains, but sandwiched between these domains was a second variablelike domain that was already rearranged in the germline (Vlj) (Figure 1a). In a recent Science paper, 2 Miller joins forces with Rossjohn and Le Nours to report that TCRl pairs with TCRc to create a heterodimeric clTCR. Crystal structures of two examples from the gray short-tailed opossum show that Vc and Vl j create a scaffold that supports the Vl domain at the membrane distal region of the receptor.…”

“…To define the architecture of a TCR containing TCRl, Morrissey et al 2 set about determining which TCR chain pairs with TCRl with a single-cell transcriptome RNA sequencing campaign. After finding no TCRl transcripts in peripheral blood T cells, they moved on to the spleen where 37% of cells contained TCRl.…”

Genetic and genomic architecture in eight strains of the laboratory opossum Monodelphis domestica

“…Marsupials are also valuable for investigating major epigenetic processes such as X-chromosome inactivation ( Hornecker et al 2007 ; Grant et al 2012 ; Rodriguez-Delgado et al 2014 ; Wang et al 2014 ; Waters et al 2018 ; Mahadevaiah et al 2020 ) and genomic imprinting ( Weidman et al 2006 ; Lawton et al 2008 ; Das et al 2012 ; Douglas et al 2014 ; Suzuki et al 2018 ). Monodelphis domestica has been used in many medical and disease studies, such as gene expression during neural development ( Dooley et al 2012 ; Sears et al 2012 ; Pavan et al 2014 ; Wheaton et al 2021 ), hypercholesterolemia and steatohepatitis ( Chan et al 2010 , 2012 ; Chan and VandeBerg 2011 ), cancer therapy and prevention ( Nair and VandeBerg 2012 ; Nair et al 2014 ), immunogenomics ( Parra et al 2008 ; Morrissey et al 2021 ; Schraven et al 2021 ), viral pathogenesis ( Thomas et al 2019 ), and influence of biological sex on social behavior, individual recognition, and associative learning ( Gil et al 2019 ).…”

Genetic and genomic architecture in eight strains of the laboratory opossumMonodelphis domestica

“…Marsupials are also valuable for investigating major epigenetic processes such as X-chromosome inactivation (Hornecker et al 2007; Grant et al 2012; Rodriguez-Delgado et al 2014; Wang et al 2014; Waters et al 2018; Mahadevaiah et al 2020) and genomic imprinting (Weidman et al 2006; Lawton et al 2008; Das et al 2012; Douglas et al 2014; Suzuki et al 2018). M. domestica has been used in many medical and disease studies, such as gene expression during neural development (Dooley et al 2012; Sears et al 2012; Pavan et al 2014; Wheaton et al 2021), hypercholesterolemia and steatohepatitis (Chan et al 2010; Chan and VandeBerg 2011; Chan et al 2012), cancer therapy and prevention (Nair and VandeBerg 2012; Nair et al 2014), immunogenomics (Parra et al 2008; Morrissey et al 2021; Schraven et al 2021), viral pathogenesis (Thomas et al 2019), and influence of biological sex on social behavior, individual recognition, and associative learning (Gil et al 2019).…”