REGULATION OF IMMUNE RESPONSES Costimulatory/Coinhibitory Molecules CD28, CTLA-4, and PD-1 J.P. Allison (USA) and T. Honjo (Japan) won 2018 Nobel Prize for their discovery of cancer therapy by inhibition of negative immune regulation. In T-cell-mediated responses, CD28 transmits a positive signal to T cells for their activation, whereas CTLA-4 (CD152) and PD-1 make negative immunosuppressive stimuli. ©V.V.Klimov