NKG2A/CD94 Is a New Immune Receptor for HLA-G and Distinguishes Amino Acid Differences in the HLA-G Heavy Chain

June 19, 2020


International Journal of Molecular Sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352787/  


The immune checkpoint molecule human leukocyte antigen (HLA)-G is upregulated on malignant cells but not on healthy surrounding cells, the requirement of understanding the basis of receptor mediated events at the HLA-G/NK cell interface becomes obvious. The NK cell receptors ILT2 and KIR2DL4 have been described to bind to HLA-G; however, their differential function and expression levels on NK cell subsets suggest the existence of an unreported receptor. Here, we performed a ligand-based receptor capture on living cells utilizing sHLA-G*01:01 molecules coupled to TriCEPS and bound to NK cells followed by mass spectrometric analyses. We could define NKG2A/CD94 as a cognate receptor of HLA-G.


Gia-Gia T. Hò, Alexander A. Celik, Trevor Huyton, Wiebke Hiemisch, Rainer Blasczyk, Gwendolin S. Simper, and Christina Bade-Doeding