Based on our observations, we hypothesize that CD4 CTLs use two additive signals to directly engage neuroblastoma cells lacking HLA Class II: first, ligation between the activating receptors NKG2C/E on CD4 CTLs and the ligand HLA-E on neuroblastoma cells, and second, CRTAM of CD4 CTLs and CADM1 on neuroblastoma cells. Here, CD4 is linked to neuroblastoma.