The activation of helper T cells by peptides bound to proteins of the class II Major Histocompatibility Complex (MHC II) is pivotal to the initiation of an immune response. The primary functional requirement imposed on MHC II proteins is the ability to efficiently bind thousands of different peptides. Structurally, this is reflected in a unique architecture of binding interactions. The peptide is bound in an extended conformation within a groove on the membrane distal surface of the protein that is lined with several pockets that can accommodate peptide side-chains. Conserved MHC II protein residues also form hydrogen bonds along the length of the peptide main-chain. Here we review recent advances in the study of peptide-MHC II protein reactions that have led to an enhanced understanding of binding energetics. These results demonstrate that peptide-MHC II protein complexes achieve high affinity binding from the array of hydrogen bonds that are energetically segregated from the pocket interactions, which can then add to an intrinsic hydrogen bond-mediated affinity. Thus, MHC II proteins are unlike antibodies, which utilize cooperativity among binding interactions to achieve high affinity and specificity. The significance of these observations is discussed within the context of possible mechanisms for the HLA-DM protein that regulates peptide presentation in vivo and the design of non-peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators.

中文翻译：

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II类主要组织相容性复合物的肽与蛋白质之间的结合相互作用。

通过与II类主要组织相容性复合物（MHC II）蛋白质结合的肽激活辅助T细胞，对于免疫应答的启动至关重要。对MHC II蛋白施加的主要功能要求是有效结合数千种不同肽的能力。从结构上讲，这反映在绑定交互的独特体系结构中。肽以延伸构象结合在蛋白质的膜远端表面上的凹槽内，该凹槽内衬有几个可容纳肽侧链的口袋。保守的MHC II蛋白残基也沿着肽主链的长度形成氢键。在这里，我们综述了肽-MHC II蛋白反应研究的最新进展，这些进展已导致人们对结合能学有了更深入的了解。这些结果表明，肽-MHC II蛋白复合物从与口袋相互作用中能量分离的氢键阵列实现了高亲和力结合，然后可以增加固有的氢键介导的亲和力。因此，MHC II蛋白不同于抗体，它利用结合相互作用之间的协同作用来实现高亲和力和特异性。这些观察结果的意义将在HLA-DM蛋白在体内调节肽呈递的可能机制以及可结合MHC II蛋白并充当疫苗或免疫调节剂的非肽分子设计的背景下进行讨论。然后可以增加固有的氢键介导的亲和力。因此，MHC II蛋白不同于抗体，它利用结合相互作用之间的协同作用来实现高亲和力和特异性。这些观察结果的意义将在HLA-DM蛋白在体内调节肽呈递的可能机制以及可结合MHC II蛋白并充当疫苗或免疫调节剂的非肽分子设计的背景下进行讨论。然后可以增加固有的氢键介导的亲和力。因此，MHC II蛋白不同于抗体，它利用结合相互作用之间的协同作用来实现高亲和力和特异性。这些观察结果的意义将在HLA-DM蛋白在体内调节肽呈递的可能机制以及可结合MHC II蛋白并充当疫苗或免疫调节剂的非肽分子设计的背景下进行讨论。