Class (II) warfare

Abstract

Immunology Natural killer (NK) cells are cytotoxic lymphocytes that recognize virus-infected, stressed cells and tumor cells with both activating and inhibitory receptors. Many NK cell receptors bind human leukocyte antigen (HLA) class I, which presents self-peptides but which is often lost within tumors and during infection. Whether and how NK cells might then bind HLA class II molecules, which are required for adaptive immunity, remains unclear. Niehrs et al. report a direct functional interaction between the NK cell receptor NKp44 and a subset of commonly expressed HLA-DP molecules, including HLA-DP401. Intriguingly, the strength of NK cell binding and activation was both peptide- and HLA allotype–dependent. This work may help explain previously reported associations between certain HLA allotypes and some autoimmune, viral, and graft-versus-host disease outcomes. Nat. Immunol. 10.1038/s41590-019-0448-4 (2019).