In my experiment design, I plan to transduce primary cells with cre recombinase prior to transplantation into immunocompetent hosts.
So understanding whether the host will mount immune response to the incoming cre recombinase is critical.
Many thanks to your expertise!
Cre recombinase is a nuclear protein, so it is unlikely that the protein inside the cell will be seen by the immune system. Even if you use the Cre-ER fusion protein, which is cytoplasmic until you add tamoxifen, it will not be seen by the immune system. Any protein that will be recognized by the immune system due to cell death and release of Cre will also not be a problem as this will not affect the viability of intact Cre expressing cells. The immune system sees cell surface proteins and sugars, or circulating proteins. So even if you were to immunize mice with recombinant Cre, they would not generate an immune response against Cre expressing cells.
Theoretically, the possibility exists, that proteosomal degradation of Cre protein will result to peptides, which can be presented by MHC class I molecules on the surface of cells. Evidently, these complexes will be "foreign" for mice not expressing Cre. I do not know exactly, how much this problem is critical in case of Cre recombinase. In case of GFP protein, this is really big problem. Immune system of H-2d mouse strains (BALB/c, DBA/2, B10.D2, etc.) see the peptide of GFP protein which is associated with H-2Kd molecule. This results in vigorous CTL response against transplanted GFP-expressing H-2d cells. This immunogenicity is less evident in H-2b mice (C57BL/6) and GFP expressing H-2b cells can survive in B6 hosts during long time. I think, anything similar will take place in case of Cre protein, and immunogenicity will depend on mouse strain.
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