Natural killer (NK) cells require cytokine signals to differentiate into fully functional effector cells that initiate protective antiviral responses . Many pathogens have evolved countermeasures to avoid interferon-mediated detection and clearance by NK cells [1,2], however, regulatory mechanisms limiting cytokine activation of NK cells that reduce non-specific tissue damage remain poorly defined. CD160 is a 27 kDa glycoprotein which was initially identified with the monoclonal antibody BY55 . Its expression is tightly associated with peripheral blood NK cells and CD8 T lymphocytes with cytolytic effector activity [2,3,4]. The cDNA sequence of CD160 predicts a cysteine-rich, glycosylphosphatidylinositol-(GPI)-anchored protein of 181 amino acids with a single Ig-like domain weakly homologous to KIR2DL4 molecule. It was found that TNF receptor herpesvirus entry mediator (HVEM) preferentially engages CD160 trimer to costimulate activation, while a viral ortholog of HVEM specifically binds to B and T lymphocyte attenuator (BTLA) to suppress this signaling. CD160 antigen is a protein that in humans is encoded by the CD160 gene. We have found that CD160 is expressed at the cell surface as a tightly disulfide-linked multimer. The homology model of CD160 antigen domain [Figure 1] shows cysteine-rich region that was found to be responsible for CD160 tight-timer formation even under reduced conditions. CD160 trimer forms stable complex with HVEM, while monomeric form refused to binds its cognate ligand. Thus, regulation of CD160 bidirectional binding may represent a common mechanism of immune regulation targeted by multiple pathogens, which by extension is a potential target for therapeutic manipulation.
IN is Marie Curie Fellow financed by Programme SASPRO, co-funded by European Union and the Slovak Academy of Sciences. The authors gratefully acknowledge the contribution of the Slovak Research and Development Agency under the project APVV-14-0839 and the contribution of the Scientific Grant Agency of the Slovak Republic under the grant 2/0103/15.