HLA-E/peptide complexes differentially interact with NKG2A/CD94 and T cell receptors.

The virtually monomorphic antigen presentation molecule HLA-E can present self- and non-self peptides to the NKG2A/CD94 co-receptor inhibitory complex expressed on natural killer (NK) cells and to T cell receptors (TCRs) expressed on T cells. HLA-E presents self-peptides to NKG2A/CD94 to regulate tissue homeostasis, whereas HLA-E restricted T cells mediate regulatory and cytotoxic responses toward pathogen-infected cells. In this study, we directly compared HLA-E/peptide recognition and signaling between NKG2A/CD94 and 2 HLA-E restricted TCRs that can recognize self-peptides or identical peptide mimics from the viral UL40 protein of cytomegalovirus using position substituted peptide variants.

Physiologically Based Pharmacokinetic Model of Tyrosine Kinase Inhibitors to Predict Target Site Penetration, with PET-Guided Verification.

Osimertinib, a tyrosine kinase inhibitor (TKI), treats non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. However, its efficacy may vary due to heterogeneous drug distribution, assessable through microdosed radiolabeled drugs and positron emission tomography (PET). Precision dosing using microdosed TKI-PET encounters challenges due to pharmacokinetic (PK) variations between micro- and therapeutic doses.

Genome-wide association study on chronic postsurgical pain in the UK Biobank.

Background: Chronic postsurgical pain (CPSP) persists beyond the expected healing period after surgery, imposing a substantial burden on overall patient well-being. Unfortunately, CPSP often remains underdiagnosed and undertreated. To better understand the mechanism of CPSP development, we aimed to identify genetic variants associated with CPSP.