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The structure of the marsupial γμ T-cell receptor defines a third T-cell lineage in vertebrates

Most T cells found in jawed vertebrates express functional heterodimeric receptors (TCRs) on their surface formed by either α and β or γ and δ chains. Each chain possesses two domains, an amino-terminal variable domain (V) and a constant domain (C) on the carboxy-terminus (V-C pattern). In most cases, the ability of T cells to recognize diverse antigens relies on the surface (or paratope) located within Vα – Vβ or Vγ – Vδ segments. Recent genomic studies of non-eutherian mammals identified clusters of genes that resemble the classical TCR loci but surprisingly contain an additional variable segment. The functional product common for marsupials and monotremes called ‘μ chain’ was predicted to contain two variable (Vμ and Vμj) and one constant (Cμ) domains. Single cells analysis of blood and spleen from Monodelphis domestica showed that some of the splenic T cells co-express the μ and γ chains suggesting that both polypeptides could form a novel type of T cell receptor, the γμTCR. Using obtained sequences, we generated and structurally characterized two different γμTCRs. Here, we present the novel and unusual architecture of a third lineage of T cell receptor found in marsupials and monotremes [1] . The molecular assembly of the marsupial T cell receptor defines a third T cell lineage. SCIENCE , 371, 1383-1388,