New vistas unfold: Chicken MHC molecules reveal unexpected ways to present peptides to the immune system.
New vistas unfold: Chicken MHC molecules reveal unexpected ways to present peptides to the immune system.
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DOI：
10.3389/fimmu.2022.886672
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
几十年来，生物化学和结构研究已经研究了各种各样的分子的功能，这些分子的结构类似于由主要组织相容性复合体（MHC）编码的经典I类和II类分子，其中人类和小鼠的许多方面现在被奉为教科书中的教条。然而，在其他有颌脊椎动物中，MHC和MHC分子有很大的变化，对家鸡的了解最详细。在鸡中的许多意想不到的特征是多态性TAP和tapasin基因与基于与典型哺乳动物相比不同的基因组排列的显性表达的I类基因之间的共进化。另一个重要的发现是I类等位基因的一系列特性，包括肽库的大小、稳定性和细胞表面表达水平，这也在人类中发现，尽管没有那么极端，并且导致了响应感染性病原体的通才和专家的概念。鸡I类分子的结构研究提供了分子解释的差异，肽结合相比，典型的哺乳动物。这些意想不到的现象包括：对于难养等位基因，在肽C-末端与三个锚残基和酸性残基的严格结合，以及对于混杂等位基因，在肽C-末端重塑结合位点、宽疏水口袋中的锚残基的松弛结合和延伸。对鸡II类分子的最初几项研究已经发现了意想不到的结构特征，包括通过十聚体核心结合肽的等位基因。通过鸡和其他非哺乳类脊椎动物的生化和结构研究，对MHC分子如何与淋巴细胞结合并将肽呈递给淋巴细胞的理解似乎会随着进一步的意外发现而大大拓宽。
The functions of a wide variety of molecules with structures similar to the classical class I and class II molecules encoded by the major histocompatibility complex (MHC) have been studied by biochemical and structural studies over decades, with many aspects for humans and mice now enshrined in textbooks as dogma. However, there is much variation of the MHC and MHC molecules among the other jawed vertebrates, understood in the most detail for the domestic chicken. Among the many unexpected features in chickens is the co-evolution between polymorphic TAP and tapasin genes with a dominantly-expressed class I gene based on a different genomic arrangement compared to typical mammals. Another important discovery was the hierarchy of class I alleles for a suite of properties including size of peptide repertoire, stability and cell surface expression level, which is also found in humans although not as extreme, and which led to the concept of generalists and specialists in response to infectious pathogens. Structural studies of chicken class I molecules have provided molecular explanations for the differences in peptide binding compared to typical mammals. These unexpected phenomena include the stringent binding with three anchor residues and acidic residues at the peptide C-terminus for fastidious alleles, and the remodelling binding sites, relaxed binding of anchor residues in broad hydrophobic pockets and extension at the peptide C-terminus for promiscuous alleles. The first few studies for chicken class II molecules have already uncovered unanticipated structural features, including an allele that binds peptides by a decamer core. It seems likely that the understanding of how MHC molecules bind and present peptides to lymphocytes will broaden considerably with further unexpected discoveries through biochemical and structural studies for chickens and other non-mammalian vertebrates.
影响因子：
7.3
作者：
Wei X;Wang S;Li Z;Li Z;Qu Z;Wang S;Zou B;Liang R;Xia C;Zhang N
通讯作者：
Zhang N