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.

αβ 和 γδ T 细胞受体 (TCR) 是高度多样化的抗原受体，定义了两个进化上保守的 T 细胞谱系。我们描述了专门在非真兽类哺乳动物中发现的 γμTCRs 群体，它们由与三域 (Vμ-Vμj-Cμ) μ 链配对的双域 (Vγ-Cγ) γ 链组成。γμTCR 的特点是 Vγ 和 Vμj 域的多样性有限，以及高度多样化的未配对 Vμ 域。两个不同的 γμTCR 的晶体结构揭示了 γμTCR 异二聚体结合的结构基础。Vμ 域具有单域抗体的特征，其中高变 CDR3μ 环表明主要抗原识别决定簇。我们在这里定义了支撑第三个 TCR 谱系 γμTCR 组装的分子基础。