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A Single-Domain TCR-like Antibody Selective for the Qa-1/Qdm Peptide Complex Enhances Tumoricidal Activity of NK Cells via Blocking the NKG2A Immune Checkpoint

J Immunol. 2022-04; 
Soroush Ghaffari, Katherine Upchurch-Ange, Susanne Gimlin, Trivendra Tripathi, Marjolein Sluijter, Jim Middelburg, Thorbald van Hall, Jon Weidanz
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Proteins, Expression, Isolation and Analysis … The Abs were captured and purified using protein A beads (GenScript, catalog no. L00210.). … Additional purified samples were run on an analytical-grade Superdex 200 column (GE … Get A Quote

摘要

The NKG2A/HLA-E axis is an immune checkpoint that suppresses immune effector activity in the tumor microenvironment. In mice, the ligand for the NKG2A/CD94 inhibitory receptor is the nonclassical MHC molecule Qa-1, the HLA-E ortholog, which presents the peptide AMAPRTLLL, referred to as Qdm (for Qa-1 determinant modifier). This dominant peptide is derived from the leader sequences of murine classical MHC class I encoded by the H-2D and -L loci. To broaden our understanding of Qa-1/Qdm peptide complex biology and its tumor protective role, we identified a TCR-like Ab from a single domain VHH library using yeast surface display. The TCR-like Ab (EXX-1) binds only to the Qa-1/Qdm peptide complex and not to Qa-1 al... More

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