Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors

Dulberger CL, et al. , 46(6):1018-1029.e7, Immunity, 2017

A major histocompatibility complex (MHC) molecule, HLA-F (human leukocyte antigen F) is involved in wide range of immunoregulatory functions by signaling through natural killer cell receptors (NKRs). Current study reports the molecular description of HLA-F and provides a model to demonstrate how peptide binding modulates HLA-F recognition by NKRs. Structural, biochemical, and evolutionary studies reveal that HLA-F can exist in an open conformer (OC) and peptide-bound state. Binding interactions between HLA-F and the inhibitory NKR, LIR1 were measured using Bio-Layer Interferometry (BLI). A Pall ForteBio BLItz instrument equipped with Streptavidin (SA) Biosensor probes was used to perform all BLI experiments. SA sensor tips were immobilized with biotinylated LIR1 protein until saturation. Subsequently, loaded sensor tips were dipped in different dilutions of HLA-F, HLA-F OC and HLA-F W62R mutant solutions. Equilibrium dissociation constants (KD values) were determined by nonlinear regression using Prism software. Overall findings of this investigation provide molecular details of HLA-F to understand how HLA-F could regulate immunity via interactions with NKRs.

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