HLA-F belongs to the non-classical HLA-Ib molecules with a marginal polymorphic nature and tissue-restricted distribution. HLA-F is a ligand of the NK cell receptor KIR3DS1, whose activation initiates an antiviral downstream immune response and lead to delayed disease progression of HIV-1. During the time course of HIV infection, the expression of HLA-F is upregulated while its interaction with KIR3DS1 is diminished. Understanding HLA-F peptide selection and presentation is essential to a comprehensive understanding of this dynamic immune response and the molecules function. In this study, we were able to recover stable pHLA-F*01:01 complexes and analyze the characteristics of peptides naturally presented by HLA-F. These HLA-F-restricted peptides exhibit a non-canonical length without a defined N-terminal anchor. The peptide characteristics lead to a unique presentation profile and influence the stability of the protein. Furthermore, we demonstrate that almost all source proteins of HLA-F-restricted peptides are described to interact with HIV proteins. Understanding the balance switch between HLA-Ia and HLA-F expression and peptide selection will support to understand the role of HLA-F in viral pathogenesis.

中文翻译：

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HLA-F * 01：01呈现具有N端柔性且优选长度为16个残基的肽。

HLA-F属于非经典HLA-Ib分子，具有边缘多态性和组织受限分布。HLA-F是NK细胞受体KIR3DS1的配体，其激活可引发抗病毒下游免疫反应并导致HIV-1疾病进展延迟。在HIV感染的过程中，HLA-F的表达被上调，而与KIR3DS1的相互作用被减弱。了解HLA-F肽的选择和呈递对于全面了解这种动态免疫应答和分子功能至关重要。在这项研究中，我们能够回收稳定的pHLA-F * 01：01复合物并分析HLA-F天然呈递的肽的特征。这些HLA-F限制性肽段具有非规范的长度，而没有定义的N末端锚点。肽的特征导致独特的呈递特征并影响蛋白质的稳定性。此外，我们证明了HLA-F限制性肽的几乎所有来源蛋白都被描述与HIV蛋白相互作用。了解HLA-1a和HLA-F表达与肽选择之间的平衡转换将有助于理解HLA-F在病毒发病机理中的作用。