CRISPR-Cas9 screening reveals a distinct class of MHC-I binders with precise HLA-peptide recognition.

Human leukocyte antigen (HLA) class-I molecules present fragments of the cellular proteome to the T cell receptor (TCR) of cytotoxic T cells to control infectious diseases and cancer. The large number of combinations of HLA class-I allotypes and peptides allows for highly specific and dedicated low-affinity interactions to a diverse array of TCRs and natural killer (NK) cell receptors. Whether the divergent HLA class-I peptide complex is exclusive for interactions with these proteins is unknown. Using genome-wide CRISPR-Cas9 activation and knockout screens, we identified peptide-specific HLA-C∗07 combinations that can interact with the surface molecules CD55 and heparan sulfate. These interactions closely resemble the HLA class-I interaction with the TCR regarding both the affinity range and the specificity of the peptide and HLA allele. These findings indicate that various proteins can specifically bind HLA class-I peptide complexes due to their polymorphic nature, which suggests there are more interactions like the ones we describe here.

Comparison of sleep deprivation and a low dose of ketamine on sleep and the electroencephalogram in Brown Norway rats.

Ketamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid, suggesting a different mode of action. A rapid antidepressant effect is also observed following sleep deprivation (SD). In the present study, we aimed to evaluate the effect of a 6-h SD and acute ketamine treatment on vigilance states, locomotor activity, and electroencephalogram (EEG) power density spectra in Brown Norway rats under constant condition over 2 recording days. After SD and after the initial waking period induced by ketamine, both treatments induced a similar increase in non-rapid eye movement (NREM) sleep and EEG slow-wave activity (SWA) in NREM sleep. Rapid eye movement (REM) sleep was reduced immediately after both treatments but was recovered later only after the SD. The effects on the waking EEG differed between the treatments, with a faster theta peak during and after SD, and no change in the waking spectrum after ketamine. In conclusion, SD and ketamine both lead to an acute increment in NREM sleep SWA as well as in a reduction in REM sleep. The results suggest that selective suppression of REM sleep, combined with enhancement of SWA during NREM may be effective in the treatment of depression.