The Role of the HLA Class I alpha 2 Helix in Determining Ligand Hierarchy for the Killer Cell Ig-like Receptor 3DL1 Philippa
Philippa M Saunders, Bruce J MacLachlan, Jacqueline Widjaja, Shu Cheng Wong, Clare VL Oates, Jamie Rossjohn, Julian P Vivian, Andrew G Brooks
The Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2021
HLA class I molecules that represent ligands for the inhibitory killer cell Ig-like receptor (KIR) 3DL1 found on NK cells are categorically defined as those HLA-A and HLA-B allotypes containing the Bw4 motif, yet KIR3DL1 demonstrates hierarchical recognition of these HLA-Bw4 ligands. To better understand the molecular basis underpinning differential KIR3DL1 recognition, the HLA-ABw4 family of allotypes were investigated. Transfected human 721.221 cells expressing HLA-A*32:01 strongly inhibited primary human KIR3DL1+ NK cells, whereas HLA-A*24:02 and HLA-A*23:01 displayed intermediate potency and HLA-A*25:01 failed to inhibit activation of KIR3DL1+ NK cells. Structural studies demonstrated th..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council (ARC)
This work was supported by a program grant from the National Health and Medical Research Council of Australia (1113293) and the Australian Research Council (ARC) (CE140100011); J.R. is supported by an Australian ARC Laureate Fellowship.