Key Points The chicken pBL2*019:01 structure reveals a conserved α- and β-chain–pairing mechanism. The variable β1 domain of chicken MHC-II determines peptide-presentation profiles. The interaction between pBL2*019:01 and CD4 differs from the corresponding pMHC-II. Visual Abstract MHC class II (MHC-II) molecules play a crucial role in cellular and humoral immunity by forming peptide–MHC-II (pMHC-II) complexes. The three-dimensional structures of pMHC-II complexes have been well resolved in humans and mice. However, there is no structural information for pMHC-II complexes in nonmammals. In chickens, there are two closely related and highly polymorphic β-chains and one monomorphic α-chain, and the mechanism by which one monomorphic α-chain combines with two polymorphic β-chains to form a functional heterodimer remains unknown. In this study, we report the crystal structure of a chicken pMHC-II complex (pBL2*019:01) at 1.9-Å resolution as the first nonmammalian structure of a pMHC-II complex. The structure reveals an increase in hydrogen bonding between the α and β main chains at the central interface that is introduced by the insertion of four residues in the α-chain. The residues in the β-chain that form hydrogen bonds with the α-chain are conserved among all β alleles. These structural characteristics explain the phenomenon of only one BLA allele without sequence variation pairing with highly diverse BLB alleles from two loci in the genome. Additionally, the characteristics of the peptide in the peptide-binding groove were confirmed. These results provide a new understanding of the pairing mechanism of the α- and β-chains in a pMHC-II complex and establish a structural principle to design epitope-related vaccines for the prevention of chicken diseases.

中文翻译：

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鸡肽-MHC II类复合物α-和β-链的新认识配对机制

关键点鸡 pBL2*019:01 结构揭示了保守的 α- 和 β- 链配对机制。鸡 MHC-II 的可变 β1 结构域决定了肽呈递谱。pBL2*019:01 和 CD4 之间的相互作用不同于相应的 pMHC-II。Visual Abstract MHC II 类 (MHC-II) 分子通过形成肽-MHC-II (pMHC-II) 复合物在细胞和体液免疫中发挥关键作用。pMHC-II 复合物的三维结构已在人类和小鼠中得到很好的解决。然而，在非哺乳动物中没有 pMHC-II 复合物的结构信息。在鸡中，有两条密切相关且高度多态的β链和一条单态α链，一条单态α链与两条多态β链结合形成功能性异二聚体的机制尚不清楚。在这项研究中，我们以 1.9 Å 的分辨率报告了鸡 pMHC-II 复合物 (pBL2*019:01) 的晶体结构，作为 pMHC-II 复合物的第一个非哺乳动物结构。该结构揭示了中心界面处 α 和 β 主链之间的氢键增加，这是通过在 α 链中插入四个残基引入的。与 α 链形成氢键的 β 链中的残基在所有 β 等位基因中都是保守的。这些结构特征解释了只有一个没有序列变异的 BLA 等位基因与来自基因组中两个基因座的高度多样化的 BLB 等位基因配对的现象。此外，还确认了肽结合沟中肽的特征。