Human CD4+ T lymphocytes play an important role in inducing potent immune responses. T cells are activated and stimulated by peptides presented in human leucocyte antigen (HLA)-class II molecules. These HLA-class II molecules typically present peptides of between 12 and 20 amino acids in length. The region that interacts with the HLA molecule, designated as the peptide-binding core, is highly conserved in the residues which anchor the peptide to the molecule. In addition, as these peptides are the product of proteolytic cleavages, certain conserved residues may be expected at the N- and C-termini outside the binding core. To study whether similar conserved residues are present in different cell types, potentially harbouring different proteolytic enzymes, the ligandomes of HLA-DRB1*03:01/HLA-DRB > 1 derived from two different cell types (dendritic cells and EBV-transformed B cells) were identified with mass spectrometry and the binding core and N- and C-terminal residues of a total of 16,568 peptides were analysed using the frequencies of the amino acids in the human proteome. Similar binding motifs were found as well as comparable conservations in the N- and C-terminal residues. Furthermore, the terminal conservations of these ligandomes were compared to the N- and C-terminal conservations of the ligandome acquired from dendritic cells homozygous for HLA-DRB1*04:01. Again, comparable conservations were evident with only minor differences. Taken together, these data show that there are conservations in the terminal residues of peptides, presumably the result of the activity of proteases involved in antigen processing.

中文翻译：

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从不同的 HLA II 类分子获得的配体在肽结合裂口外的 N 端和 C 端残基上是同源的。


人类 CD4+ T 淋巴细胞在诱导有效的免疫反应中发挥着重要作用。 T 细胞被人类白细胞抗原 (HLA) II 类分子中的肽激活和刺激。这些 HLA-II 类分子通常呈现长度在 12 到 20 个氨基酸之间的肽。与 HLA 分子相互作用的区域被称为肽结合核心，在将肽锚定到分子上的残基中高度保守。此外，由于这些肽是蛋白水解裂解的产物，因此在结合核心之外的 N 端和 C 端可能会有某些保守残基。为了研究相似的保守残基是否存在于不同的细胞类型中，可能含有不同的蛋白水解酶，HLA-DRB1*03:01/HLA-DRB > 1 的配体来自两种不同的细胞类型（树突状细胞和 EBV 转化的 B 细胞）。通过质谱法鉴定，并使用人类蛋白质组中氨基酸的频率分析了总共 16,568 个肽的结合核心以及 N 和 C 末端残基。在 N 端和 C 端残基中发现了类似的结合基序以及类似的保守性。此外，将这些配体组的末端保守性与从 HLA-DRB1*04:01 纯合树突细胞获得的配体组的 N 端和 C 端保守性进行比较。同样，类似的保护很明显，只有很小的差异。总而言之，这些数据表明肽的末端残基存在保守性，这可能是参与抗原加工的蛋白酶活性的结果。