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

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. γμ...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2021-03, Vol.371 (6536), p.1383-1388
Main Authors: Morrissey, Kimberly A, Wegrecki, Marcin, Praveena, T, Hansen, Victoria L, Bu, Lijing, Sivaraman, Komagal Kannan, Darko, Samuel, Douek, Daniel C, Rossjohn, Jamie, Miller, Robert D, Le Nours, Jérôme
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Assembly
Cell Lineage
Chains
Complementarity Determining Regions - chemistry
Crystal structure
Crystallography, X-Ray
Domains
Lymphocytes
Lymphocytes T
Marsupials
Models, Molecular
Monodelphis - genetics
Monodelphis - immunology
Nanobodies
Protein Conformation
Protein Domains
Protein Multimerization
Receptors
Receptors, Antigen, T-Cell - chemistry
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Antigen, T-Cell, gamma-delta
Recognition
Sharks
Spleen
T cell receptors
T-Lymphocyte Subsets - immunology
Vertebrates
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abe7070