鸡 MHC I 类分子 BF2*21:01 高度复杂肽基序背后的简化原则
Simplifying principles underlying the highly complex peptide motif of the promiscuous chicken MHC class I molecule, BF2*21:01
鸡 B21 单倍型的高混杂性 MHC I 类分子 BF2*21:01 通过重塑肽结合位点结合广谱多肽，其肽基序的简化原则由体外重折叠实验、热稳定性测定、晶体结构解析与 B21 细胞系免疫肽组学分析共同揭示。该分子可容纳 P2 与 Pc-2 位点锚定残基的多种组合，并在 Pc 位点接受若干疏水氨基酸。但研究同时发现其对特定肽长度、三个锚定位点的特定氨基酸以及 P2 与 Pc-2、P3 与 Pc-3 的特定氨基酸组合存在明显偏好，由此产生高频主要肽，同时仍保留呈现广谱肽库的可能。这些简化原则有望用于预测与该高混杂性分子稳定结合的病原体肽，并为更精细的肽预测方法提供数据。
来源：eLife · doi.org
In chickens and humans, classical class I molecules of the major histocompatibility complex (MHC) have a spectrum of correlated properties, including cell surface expression and peptide repertoire. Understanding the impact of these promiscuous generalists and fastidious specialists is of considerable interest. The promiscuous BF2 molecule from the chicken B21 haplotype, BF2*21:01, binds a wide range of peptides by remodelling the peptide-binding site, allowing co-variation of the anchor residues at peptide positions P 2 and P c-2 , and binding of an anchor residue at Pc. Using in vitro refolding assays with peptides and peptide libraries, determining thermostability and crystal structures, and analysing a chicken B21 cell line by immunopeptidomics, we found that BF2*21:01 will accommodate many possible combinations at P 2 and P c-2 , as well as several hydrophobic amino acids at P c . However, marked preferences for particular peptide lengths, particular amino acids at the three anchor residues, and particular combinations of amino acids at P 2 and P c-2 as well as at P 3 and P c-3 together lead to high frequencies of major peptides while still allowing the possibility of presenting a wide peptide repertoire. These simplifying principles may eventually allow predictions of pathogen peptides with stable binding for this iconic promiscuous class I molecule, as well as providing the data for more sophisticated peptide prediction methods.