Abstract
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.
Highlights
Human leukocyte antigens (HLA) are key regulators of the immune system that scan the intracellular proteome and present self- or non-self-peptides to cells of the immune system (Klein and Sato 2000a)
Ten peptide source proteins could be confirmed by full proteome analysis (Fig. 2), while 3 peptide source proteins could not be detected by full proteome analysis
HLA-F is directly involved in immune functions during HIV-1 infection and confers a beneficial effect on disease outcome
Summary
Human leukocyte antigens (HLA) are key regulators of the immune system that scan the intracellular proteome and present self- or non-self-peptides to cells of the immune system (Klein and Sato 2000a). HLA molecules constitute highly specific ligands for T cell receptor, since every single bound peptide alters the accessible surface for immune recognition of effector cells. The exclusive interactions between a T cell receptor and a peptide-HLA-Ia (HLA-A, HLA-B and HLA-C) complex are crucial to maintain the surveillance of cellular health (Zinkernagel and Doherty 1974). The HLA-F expression pattern is highly specific. HLA-F is mainly expressed in leukocytes, including monocytes, B cells, T cells, and NK cells (Lee et al 2010). HLA-F has been detected in non-small-cell-lung cancer (Lin et al 2011), in esophageal squamous cell carcinoma (Zhang et al 2013), gastric adenocarcinoma (Ishigami et al 2013), and breast cancer (Harada et al 2015)
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