Abstract: Type I membrane proteins heterodimers are provided. Accordingly, there is provided a heterodimer comprising two polypeptides selected from the group consisting of SIRPalpha, PD1, TIGIT, LILRB2 and SIGLEC10, wherein each of the two polypeptides is capable of binding a natural binding pair thereof, and wherein the heterodimer does not comprise an amino acid sequence of a type II membrane protein capable of binding a natural binding pair thereof. Also provided are nucleic acid constructs and systems encoding the heterodimer, host-cells expressing same and methods of use thereof.

Abstract: Heterodimers are provided. Accordingly, there is provided a heterodimer comprising a dimerizing moiety attached to at least one amino acid sequence of at least one type I membrane protein capable of at least binding a natural ligand or receptor of said at least one type I membrane protein and to at least one amino acid sequence of at least one type II membrane protein capable of at least binding a natural ligand or receptor of said at least one type II membrane protein. Also provided are nucleic acid constructs and systems encoding the heterodimer, host-cells expressing same and methods of use thereof.