Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775-7000, USA.
Immunol Res. 2013 May;56(1):85-95. doi: 10.1007/s12026-012-8342-2.
The adaptive immune response starts when CD4+ T cells recognize peptide antigens presented by class II molecules of the Major Histocompatibility Complex (MHCII). Two outstanding features of MHCII molecules are their polymorphism and the ability of each allele to bind a large panoply of peptides. The ability of each MHCII molecule to interact with a limited, though broad, range of amino acid sequences, or "permissive specificity" of binding, is the result of structural flexibility. This flexibility has been identified through biochemical and biophysical studies, and molecular dynamic simulations have modeled the conformational rearrangements that the peptide and the MHCII undergo during interaction. Moreover, there is evidence that the structural flexibility of the peptide/MHCII complex correlates with the activity of the "peptide-editing" molecule DM. In light of the impact that these recent findings have on our ability to predict MHCII epitopes, a review of the structural and thermodynamic determinants of peptide binding to MHCII is proposed.
适应性免疫反应始于 CD4+T 细胞识别主要组织相容性复合体 (MHCII) 类 II 分子呈递的肽抗原。MHCII 分子的两个突出特点是其多态性和每个等位基因结合大量肽的能力。每个 MHCII 分子与有限但广泛的氨基酸序列相互作用的能力，或结合的“允许特异性”，是结构灵活性的结果。这种灵活性已通过生化和生物物理研究确定，分子动力学模拟模拟了肽与 MHCII 相互作用过程中发生的构象重排。此外，有证据表明肽/MHCII 复合物的结构灵活性与“肽编辑”分子 DM 的活性相关。鉴于这些最新发现对我们预测 MHCII 表位的能力的影响，建议对肽与 MHCII 结合的结构和热力学决定因素进行综述。
